Journal of Natural Medicines最新文献

{"title":"Apoptosis- and ferroptosis-inducing activity of triptolide in SBC-3 human small-cell lung cancer cells","authors":"Tomoki Iguchi,&nbsp;Yoshihiro Mimaki","doi":"10.1007/s11418-026-02032-7","DOIUrl":"10.1007/s11418-026-02032-7","url":null,"abstract":"<div><p>Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid progression, poor prognosis, and a high recurrence rate following chemotherapy. Despite recent advances in immunotherapy, treatment options remain limited, underscoring the urgent need for novel anticancer agents. Triptolide, a natural diterpenoid, has been reported to exhibit cytotoxic activity against various cancer cell lines. However, its effects on SCLC cells, particularly its ferroptosis-inducing activity, remain largely unknown. In this study, we investigated the cytotoxic, apoptotic, and ferroptotic activities of triptolide in SBC-3 human SCLC cells. Triptolide exhibited potent dose- and time-dependent cytotoxicity and induced apoptosis through both intrinsic and extrinsic pathways, as evidenced by activation of caspases-3, -8, and -9, a decreased Bcl-2/Bax ratio, Bid cleavage, mitochondrial membrane depolarization, and excessive reactive oxygen species generation. Notably, triptolide induced ferroptosis through multiple mechanisms of action, including suppression of the p62-Nrf2 antioxidant axis, leading to decreased xCT and glutathione peroxidase 4 expression, upregulation of cellular iron uptake via increased transferrin and CD71 expression, and induction of lipid peroxidation. Triptolide also induced autophagy in SBC-3 cells, which may contribute to ferroptosis via ferritinophagy. Furthermore, triptolide demonstrated synergistic cytotoxic effects when combined with cisplatin or etoposide. To our knowledge, this study is the first to provide evidence that triptolide simultaneously induces apoptosis and ferroptosis in SCLC cells. These findings highlight triptolide as a promising therapeutic candidate for SCLC treatment, at least based on in vitro studies, particularly when combined with conventional chemotherapeutic agents.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"758 - 775"},"PeriodicalIF":2.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Processed phellodendri Chinensis cortex attenuates diabetic nephropathy via ferroptosis inhibition through GPX4/SLC7A11/Nrf2/HO-1 signaling pathway","authors":"Yue Zhou,&nbsp;Gui Xu,&nbsp;Wenjing Ren,&nbsp;Yang Chen,&nbsp;Shiru Jiang,&nbsp;Shuo Zhang,&nbsp;Xiutong Ge,&nbsp;Hui Gao,&nbsp;Fan Zhang","doi":"10.1007/s11418-026-02042-5","DOIUrl":"10.1007/s11418-026-02042-5","url":null,"abstract":"<p>Diabetic nephropathy (DN) is a common complication of diabetes, increasingly linked to ferroptosis as an important underlying mechanism. While <i>Phellodendri chinensis</i> Cortex (PC) has shown renoprotective promise, the therapeutic value of its processed products remains unclear. We therefore compared raw PC (RPC) with three processed derivatives—salt-processed PC (SPC), salt praeparatum-processed PC (SP-PC), and depositum urinae praeparatum-processed PC (DUP-PC)—to evaluate whether processing enhances anti-ferroptotic activity and DN protection. UPLC-Q-TOF-MS profiling identified 51 chemical constituents, dominated by alkaloids in positive-ion mode and phenolic acids in negative-ion mode. In high-glucose-challenged HK-2 cells, SP-PC and SPC significantly outperformed RPC, demonstrating markedly enhanced inhibition of ferroptosis by lowering malondialdehyde (MDA), <i>Fe</i>²⁺, and reactive oxygen species (ROS) while restoring glutathione (GSH) and up-regulating key pathway components GPX4, SLC7A11, Nrf2, and HO-1. These findings were mirrored in streptozotocin (STZ)-plus-high-fat-diet DN rats, where SP-PC and SPC more effectively reduced serum creatinine (S-Cr), blood urea nitrogen (BUN), microalbumin-to-albumin ratio (MAU/ALB) and attenuated renal ferroptosis markers. Critically, both cellular and animal experiments consistently revealed that processing significantly enhances the anti-ferroptotic activity of PC. Thus, processed PC products—especially SP-PC and SPC—confer superior protection against DN by more effectively inhibiting ferroptosis via the GPX4/SLC7A11/Nrf2/HO-1 axis, highlighting processing as a key strategy to boost anti-ferroptotic efficacy in renal protection.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"776 - 796"},"PeriodicalIF":2.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota mediates the antidepressant-like effects of xiaochaihutang: mechanisms involving inhibition of inflammation and enhancement of barrier function","authors":"Jie Pang,&nbsp;Xingjiao Ma,&nbsp;Nian Hong,&nbsp;Zheng Shen,&nbsp;Shile Li,&nbsp;Xinwei Li,&nbsp;Shasha Wang,&nbsp;Huan Cong,&nbsp;Kuo Zhang,&nbsp;Jingyu Yang,&nbsp;Chunfu Wu","doi":"10.1007/s11418-026-02037-2","DOIUrl":"10.1007/s11418-026-02037-2","url":null,"abstract":"<div><p>Depression is a common mental disorder that seriously impairs the psychological and physical health of patients. Extensive research has indicated that patients with depression exhibit disturbances in their gut microbiota. Xiaochaihutang (XCHT) is a traditional herbal recipe widely used in China, and previous studies have found it to possess antidepressant properties. However, whether XCHT can modulate depression-associated gut microbiota dysbiosis remains unclear. In this research, we investigated the impact of XCHT on the microbiota-gut-brain axis in depressed rats and elucidated the potential mechanisms. A rat model of depression was established using the chronic unpredictable mild stress (CUMS) protocol. Behavioral tests demonstrated that XCHT significantly alleviated depression-like behaviors. 16S rRNA sequencing revealed that XCHT enhanced the diversity and compositional structure of the gut microbiota and specifically increased the abundance of the beneficial bacterium <i>Blautia</i>. Fecal microbiota transplantation (FMT) experiments further confirmed that the antidepressant-like effects of XCHT were mediated through modulation of the gut microbiota. Furthermore, XCHT exhibited anti-inflammatory properties in both the central and peripheral systems and improved the integrity of the intestinal barrier and the blood-brain barrier. These mechanisms were also validated using the FMT approach. Collectively, these findings suggest that the antidepressant-like mechanism of XCHT may be directly linked to the regulation of the microbiota-gut-brain axis. This study demonstrates that XCHT exerts antidepressant-like effects by modulating the microbiota-gut-brain axis, providing novel insights into the potential therapeutic mechanisms and clinical applications for depression.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"881 - 898"},"PeriodicalIF":2.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocarpinensis A–B: two novel cycloartane triterpenoids isolated from Monocarpia kalimantanensis and their medicinal evaluation","authors":"Fahriani Istiqamah,&nbsp;Wahyu Safriansyah,&nbsp;Endang Juliansyah,&nbsp;Sari Purbaya,&nbsp;Fajar Fauzi Abdullah,&nbsp;Rustaman Rustaman,&nbsp;Josephine Elizabeth Siregar,&nbsp;Hadi Kuncoro,&nbsp;Kai Oppel,&nbsp;Ronny Lesmana,&nbsp;Yudha Prawira Budiman,&nbsp;Unang Supratman","doi":"10.1007/s11418-026-02027-4","DOIUrl":"10.1007/s11418-026-02027-4","url":null,"abstract":"<div><p><i>Monocarpia kalimantanensis</i> (Annonaceae) is often used by indigenous communities in East Kalimantan, Indonesia, but information on its chemical composition and biological activity remains limited. Therefore, this study aims to isolate two new monocarpin derivatives from <i>n</i>-hexane extracts of <i>M. kalimantanensis</i> bark, namely monocarpinensis A (<b>1</b>) and monocarpinensis B (<b>2</b>), as well as one known cycloartane-type triterpenoid (<b>3</b>). The structures of these new compounds were determined through comprehensive spectroscopic analysis, including HRTOF-MS, 1D and 2D NMR, IR, UV, and ECD, supported by TD-DFT calculations. All isolated compounds were tested for ex vivo antiplasmodial activity, and compounds <b>1–3</b> were evaluated against MCF-7 and normal CV-1 cell lines using PrestoBlue method. The cytotoxicity assay showed that monocarpinensis A (<b>1</b>) had the lowest IC₅₀ values of 126.5 and 520.2 µM against MCF-7 and CV-1 cell lines, respectively. However, compounds <b>1–3</b> did not show significant antiplasmodial activity. The current study is the first to report monocarpin derivatives from <i>M. kalimantanensis</i> and their evaluations as potential anticancer and antiplasmodial candidates.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"858 - 866"},"PeriodicalIF":2.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated network pharmacology and pharmacological evaluation to elucidate the effect and mechanism of the novel combination PMS in treatment of osteoporosis","authors":"Qingchang Wu,&nbsp;Yachen Wang,&nbsp;Lijin Yang,&nbsp;Runcong Dong,&nbsp;Yuxu Xie","doi":"10.1007/s11418-025-01973-9","DOIUrl":"10.1007/s11418-025-01973-9","url":null,"abstract":"<div><p>Psoralen, magnoflorine and sweroside were main active components of Xian-Ling-Gu-Bao capsule. PMS (a combination of psoralen, magnoflorine and sweroside at extremely low concentration), exhibited excellent promoting osteoblastic activity on pre-osteoblastic MC3T3-E1 cells in our previous work, and has been filed as a patent in China. However, the effect and mechanism of PMS for anti-osteoporosis at present remain unclear. Therefore, further exploring the potential anti-osteoporosis mechanism of PMS to strongly provide more evidences for developing as a novel derivative drug. In the present study, in vivo experiments were conducted to evaluate anti-osteoporosis action of PMS by using zebrafish model, and PMS treatment could significantly inhibit dexamethasone-induced osteoporosis in zebrafish. Subsequently, the data of network pharmacology and the intracellular concentrations of each ingredient further analyzed GPR30/PI3K/AKT signaling pathway probably involved in PMS-induced osteoblastic activity. Importantly, the results of western blot exhibited that PMS could increase the expressions of the membrane receptor GPR30, <i>p</i>-PI3K/PI3K and <i>p</i>-AKT/AKT on MC3T3-E1 cells, while PMS-induced osteoblastic differentiation and these protein expressions on MC3T3-E1 cells were partially blocked by the GPR30 antagonist. Collectively, our study for the first time proposed that the novel combination PMS might increase osteoblastic activity to improve osteoporosis via activating GPR30/PI3K/AKT signaling pathway, which offered a unique perspective on the mechanistic pathways of PMS in alleviating osteoporosis.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><img></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"555 - 564"},"PeriodicalIF":2.5,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in progress of natural anticoagulant active substances","authors":"Meilian Zhong,&nbsp;Xiao Liu,&nbsp;Juting Liao,&nbsp;Yang Zhang,&nbsp;Youbin Li,&nbsp;Shuojin Wang","doi":"10.1007/s11418-026-02013-w","DOIUrl":"10.1007/s11418-026-02013-w","url":null,"abstract":"<div><p>Thrombotic diseases pose a serious threat to human life and health. Anticoagulant drugs are used to treat and prevent thrombotic diseases. However, although the anticoagulant drugs currently used in clinical practice are effective, they have limitations such as narrow therapeutic window and high risk of bleeding. Therefore, the development of new safe and effective anticoagulants based on natural products and their structural modifications has become an important research direction to overcome the current treatment bottlenecks in this field. In this paper, “thrombotic diseases”, “anticoagulant-active molecules”, “natural products” and “structural modifications” were used as keywords to search the research data on anticoagulant-active molecules published in the past decade in PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases. The research progress of anticoagulant- active molecules from animals and plants was reviewed, which provide basic data for promoting the development of innovative anticoagulant drugs. In this paper, the classification of thrombotic diseases and the clinical drugs currently used in clinical practice are reviewed. Next, the coagulation mechanism and the fact that an imbalance between coagulation and anticoagulation in vivo can lead to thrombosis are described. Finally, the research reports on anticoagulant active compounds and their structural modifications from plants and animals in the past 10 years are summarized. A total of 68 anticoagulant molecules were identified, which provide an important direction and candidate molecules for the development of new, efficient and low-risk anticoagulant drugs.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"513 - 529"},"PeriodicalIF":2.5,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-asthmatic effects and ingredient annotation of the active fraction from Ganoderma lucidum","authors":"Ning Li,&nbsp;Qian He,&nbsp;Cunwu W. Chen,&nbsp;Qun Zhao,&nbsp;Yanfei F. He","doi":"10.1007/s11418-025-01978-4","DOIUrl":"10.1007/s11418-025-01978-4","url":null,"abstract":"<div><p>This research aims to screen the active fraction and explore the action mechanism of <i>Ganoderma lucidum</i> to combat asthma using asthmatic mice induced by OVA. In this study, three <i>Ganoderma lucidum</i> fractions, including GLEF40, GLEF60, and GLEF100, were obtained through the separation of D101 macroporous adsorption resin. The result of the anti-asthmatic effects illustrated that GLEFs significantly reduce Th2- and Th1- cytokines, together with chemokines MIP-1α and MDC in bronchoalveolar lavage fluid (BALF) in asthmatic mice. Among the three fractions, GLEF100 demonstrated the most potent anti-inflammatory effect. Besides, GLEF100 significantly reduced IgE levels in asthmatic mice (<i>P</i> &lt; 0.001). Further analysis found that GLEF100 significantly reduced Myd88 protein levels and strongly inhibits the expression of phosphorylated ERK, phosphorylated JNK and NF-κB p65. To further explore the Anti-asthmatic active component <i>Ganoderma lucidum</i>, a total of 92 chemical components from GLE100 was annotated using the HPLC–Q-TOF–MS/MS. In conclusion, GLEF100 effectively relieving asthma symptoms by inducing balanced Th1/Th2 immunity and inhibiting TLR4/Myd88-NF-κB-MAPKs signaling pathway. These findings highlight the potential anti-asthmatic effects of GLEF 100 and lay the foundation for further identification of the anti-asthmatic active components of <i>Ganoderma lucidum</i>.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"565 - 582"},"PeriodicalIF":2.5,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of extraction methods on the phase, composition, bacteriostatic effect of Radix Scutellariae-Rhizoma Coptidis decoction","authors":"Mei Zhang,&nbsp;Miaomiao Wei,&nbsp;Xiaolu Liu,&nbsp;Ruihua Qi,&nbsp;Min Li,&nbsp;Yunhong Wang,&nbsp;Junxuan Yang,&nbsp;Xiumei Ke","doi":"10.1007/s11418-026-02019-4","DOIUrl":"10.1007/s11418-026-02019-4","url":null,"abstract":"<div><p>The traditional co-decoction method of <i>Radix Scutellariae</i>-<i>Rhizoma Coptidis</i> generates amounts of supramoleculars and aggregation into flocculent precipitates. Modern industrial production separates them to prevent this, reflecting the conflict between modern and traditional extraction processes. This study compared the separate decoction method (modern method) and the co-decoction method (traditional method) to evaluate their effects on the phase, composition, and antibacterial efficacy of <i>Radix Scutellariae</i>-<i>Rhizoma Coptidis</i> decoction. Results showed that co-decoction altered the macroscopic and microscopic morphology of substances. Spectral and ultra-high performance liquid chromatography quadrupole time-of-light/mass spectrometry analysis indicated the phase difference resulted from supramoleculars formed by interactions between <i>Radix Scutellariae</i> and <i>Rhizoma Coptidis</i> components. High performance liquid chromatography revealed that the contents of baicalin, berberine, wogonoside, baicalein, and wogonin in the separated decoction were significantly higher than in co-decoction. Conversely, the co-decoction supramolecular precipitates exhibited significantly higher concentrations of baicalin and berberine than the co-decoction supernatant, suggesting that free components were consumed by supramoleculars. Additionally, prolonged storage and low temperature promoted the redistribution of components into the supramoleculars. Biological evaluation showed that all samples inhibited the growth of <i>E.coli</i> and <i>S.aureus</i>, with <i>Rhizoma Coptidis</i> exhibiting the strongest activity, followed by co-decoction, separated decoction, co-decoction supramolecular precipitates, <i>Radix Scutellariae</i>, and co-decoction supernatant. This demonstrates that supramoleculars can also serve as effective components. In summary, regulating the extraction process alters the physical state of the decoction, promotes component redistribution, and maintains efficacy despite a reduction in the free component content, helping to clarify the conflict between traditional and modern extraction methods and explaining the scientific connotation of Chinese medicine compatibility.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"691 - 708"},"PeriodicalIF":2.5,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological activity of isomalabaricane compounds from the marine sponge Rhabdastrella globostellata","authors":"Ekaterina A. Yurchenko,&nbsp;Anastasia B. Kozhushnaya,&nbsp;Sophia A. Kolesnikova,&nbsp;Ekaterina A. Chingizova,&nbsp;Ekaterina S. Menchinskaya,&nbsp;Evgeny A. Pislyagin,&nbsp;Aleksandra S. Kuzmich,&nbsp;Dmitry L. Aminin","doi":"10.1007/s11418-026-02030-9","DOIUrl":"10.1007/s11418-026-02030-9","url":null,"abstract":"<div><p>This study aimed to investigate the cytotoxic effects of isomalabaricane stellettins Q-V and globostelletins K-N, recently isolated from the Vietnamese marine sponge <i>Rhabdastrella globostellata</i>, against human cervical cancer HeLa, human melanoma SK-Mel-28, murine neuroblastoma Neuro-2a cells, human normal keratinocytes HaCaT, and rat normal cardiomyocytes H9c2, as well as to study the cardioprotective activity of non-toxic compounds. Stellettins Q and R and globostelletins M and N showed moderate cytotoxic activity against HeLa, SK-Mel-28, Neuro-2a cells as well as normal keratinocytes HaCaT and normal cardiomyocytes H9c2. Stellettin U increased the viability of H9c2 cardiomyocytes treated with nutrient deprivation, high concentration of ATP, TNF-α pro-inflammatory cytokine, and CoCl₂-mimicking hypoxia. In an in vitro ischemia model, stellettin U reversed mitochondrial ROS and cardiolipin peroxidation levels. In CoCl₂-induced toxicity, intracellular and mitochondrial ROS production, mitochondrial membrane depolarization, and cardiolipin peroxidation levels were normalized following stellettin U treatment. The effect of stellettin U on ATP-induced Ca²⁺influx led to the assumption that stellettin U protects cardiomyocytes via a P2X7R-dependend pathway. Moreover, the modulation of the NF-κB-dependent anti-inflammatory pathway by stellettin U was confirmed. Thus, it was suggested that stellettin U may protect cardiomyocytes via both canonical NF-κB- and non-canonical P2X7R-dependend pathways.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"867 - 875"},"PeriodicalIF":2.5,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanism of the water layer extract of Cichorium pumilum Jacq water extract in the treatment of Hepatic fibrosis was investigated using HPLC-MS/MS and network pharmacology","authors":"Weijun Chen,&nbsp;Nuan Dong,&nbsp;Xue Lu,&nbsp;Dongmei Qin","doi":"10.1007/s11418-026-02024-7","DOIUrl":"10.1007/s11418-026-02024-7","url":null,"abstract":"<div><p>Hepatic fibrosis (HF) represents a critical stage in the progression of chronic liver disease, for which effective treatments remain limited. <i>Cichorium pumilum Jacq</i> (CG), a traditional Chinese medicinal herb abundant in Xinjiang, is commonly used by the local Uyghur population for therapeutic purposes. Modern pharmacology indicates that CG possesses anti-fibrotic, anti-steatotic, anti-inflammatory, and antibacterial properties. However, the primary chemical constituents of <i>Cichorium pumilum Jacq</i> water extract (CGEF) and its anti-fibrotic mechanisms remain unclear. This study induced HF in SD rats using 40% carbon tetrachloride-olive oil and found that CGEF improved serum markers and mitigated hepatic pathological damage. CGEF components were identified via HPLC-MS/MS, with network pharmacology predicting key targets and enrichment analysis conducted. A total of 72 major compounds were identified, network pharmacology predicted 45 key targets, and enrichment results indicated CGEF may alleviate HF through a regulatory network centered on the TGF-β/Smad pathway. To validate this hypothesis, immunohistochemical analysis was performed on liver tissues from experimental animals. In vitro, TGF-β-induced HSC-T6 cell models were treated with CGEF to evaluate changes in TGF-β/Smad pathway-related gene expression. Immunohistochemical results indicated that CGEF significantly downregulated TGF-β1, TLR4, and α-SMA expression. In cell experiments, CGEF significantly reduced the gene expression of Smad2, Smad3, Smad7, TGF-β1, and PPP5C at 24 h. At 48 h, CGEF decreased the gene expression of Smad2, Smad3, TGF-β1, and PPP5C while increasing the gene expression of Smad7. Thus, CGEF may alleviate HF primarily by regulating the TGF-β/Smad pathway.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"844 - 857"},"PeriodicalIF":2.5,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}