FitoterapiaPub Date : 2025-10-02DOI: 10.1016/j.fitote.2025.106917
Vitor de Souza Mazucato , Ludmilla Tonani , Marcia Regina von Zeska Kress , Adriano Defini Andricopulo , Gisele Barbosa , Renata Krogh , Leonardo Luiz Gomes Ferreira , Natasha Marques Cassani , Bruna Coelho Sandim , Ana Carolina Gomes Jardim , Paulo Cezar Vieira
{"title":"Exploring the bioactivity potential of fruit-associated fungi: Antifungal, antiparasitic, and antiviral activities of natural extracts","authors":"Vitor de Souza Mazucato , Ludmilla Tonani , Marcia Regina von Zeska Kress , Adriano Defini Andricopulo , Gisele Barbosa , Renata Krogh , Leonardo Luiz Gomes Ferreira , Natasha Marques Cassani , Bruna Coelho Sandim , Ana Carolina Gomes Jardim , Paulo Cezar Vieira","doi":"10.1016/j.fitote.2025.106917","DOIUrl":"10.1016/j.fitote.2025.106917","url":null,"abstract":"<div><div>This study investigated the potential of fungi associated with protease-rich fruits, such as papaya and pineapple, as sources of bioactive extracts. Fungal strains were cultivated in different media (rice, corn, wheat, oats, and sugarcane bagasse. The resulting extracts were analyzed by <sup>1</sup>H NMR for chemical profiling, which allowed the observation of compounds such as rhizosolaniol, haematocin, beauvericin, cyclosporines, and fusaridioic acid. The extracts cultivated on rice exhibited high papain inhibitory activity, particularly those from <em>Neofusicoccum ribis</em> (99.4 % inhibition at 50 μg/mL) and <em>Fusarium sacchari</em> (89.6 % at 50 μg/mL). Additionally, promising anti-<em>Trypanosoma</em> (71.6 % inhibition) and antiviral (98 % inhibition of ZikV) activities were observed for the extract of <em>Fusarium verticillioides</em>, suggesting that papain can be an effective model for discovering compounds with therapeutic potential in protease-mediated diseases. Antifungal activity against <em>Candida</em> spp. was also observed in extracts cultivated on corn, specifically those from <em>Fusarium petroliphilum</em> and <em>F. sacchari</em>. Overall, these results highlight the biotechnological and pharmacological potential of fruit-associated fungi, opening new perspectives for the discovery of novel bioactive natural compounds.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106917"},"PeriodicalIF":2.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FitoterapiaPub Date : 2025-10-02DOI: 10.1016/j.fitote.2025.106906
Xiliang Yang , Qianqian Bao , Shaoyujia Xiao , Manni Pan , Die Hu , Jingyang Zhou , Yilan Hu , Binjie Zhao , Jue Jiang , Peng Ye
{"title":"Anti-colorectal cancer bioactive metabolites from endophytic fungi of Pyrola spp. targeting p-ATM/P53 pathway driven by in vitro experiments and network pharmacology","authors":"Xiliang Yang , Qianqian Bao , Shaoyujia Xiao , Manni Pan , Die Hu , Jingyang Zhou , Yilan Hu , Binjie Zhao , Jue Jiang , Peng Ye","doi":"10.1016/j.fitote.2025.106906","DOIUrl":"10.1016/j.fitote.2025.106906","url":null,"abstract":"<div><div>Employing the OSMAC (One Strain Many Compounds) strategy, a systematic investigation was conducted on secondary metabolites produced by the co-culture of endophytic fungi <em>Penicillium soppii</em> and <em>Penicillium solitum</em> isolated from <em>Pyrola</em> spp., leading to the isolation of ten compounds from their fermented products. Asperphenamate (<strong>5</strong>) amid all the compounds exhibited stronger anti-colorectal cancer (CRC) activity against HCT-8 cells than the positive control 5-fluorouracil (<em>P</em> < 0.05), significantly reducing the migration rate of HCT-8 cells in a wound healing assay, increasing the percentage of apoptotic cells from 28.13 ± 0.85 % to 45.58 ± 2.01 % as determined by live/dead cell staining assay, and blocking cell cycle progression from G1 to S phase analyzed by flow cytometry. Asperphenamate (<strong>5</strong>) may induce apoptosis or cell cycle arrest by activating the DNA damage response (DDR) as evidenced by significant enrichment of DDR-associated signaling pathways and strong binding affinity to key DDR-related proteins through network pharmacology and docking analyses. Furthermore, Asperphenamate (<strong>5</strong>) increased the expression of p53 and phosphorylated ATM (p-ATM) proteins and decreased CDK2 levels in a concentration-dependent manner, indicating it may be mediated by regulation of the ATM/p53/CDK2 signaling axis, resulting in cell cycle arrest or apoptosis. Collectively, these findings established Asperphenamate (<strong>5</strong>) as a viable lead compound for CRC therapy and underscored <em>Penicillium</em> spp. as a prolific source of bioactive natural products with medicinal properties.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106906"},"PeriodicalIF":2.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanism analysis of Salvia miltiorrhiza Bunge (Danshen) on circadian rhythm for treating myocardial injury by mathematic model.","authors":"Xiaoqian Huo, Liansheng Qiao, Jianing Zhang, Yanling Zhang, Jiwang Zhang","doi":"10.1016/j.fitote.2025.106782","DOIUrl":"10.1016/j.fitote.2025.106782","url":null,"abstract":"<p><strong>Aim of the study: </strong>Salvia miltiorrhiza Bunge (Danshen, SMB) is commonly used in the treatment of myocardial injury in cardiovascular and cerebrovascular diseases. In recent research, circadian rhythm disruption was identified as a potential reason of myocardial injury. In this study, we investigated the mechanism of SMB and its components exerting protective effect on myocardial injury through circadian rhythms pathway.</p><p><strong>Materials and methods: </strong>The myocardial injury protection and regulation mechanism of circadian rhythm of SMB was discovered in the myocardial injury model of SD rats. SMB and its components on circadian rhythm regulation was based on the rhythm gene curve fitting. Synergistic action of multiple SMB components in circadian rhythm regulation was analyzed by system dynamics modelling.</p><p><strong>Results: </strong>SMB improved hemorheological indicators. Pathway were significantly enriched in myocardial tissue of SMB-treated myocardial injury rats through module analysis of protein interaction network. Regulation of circadian gene Arntl and Per1 expression by SMB extracts was analyzed in transcriptomics and the results shows that the SMB extracts can adjust the rhythm to normal state. The effects of eight major SMB components on the gene expression were detected by rhythmic gene expression profiling in myocardial injury model of H9c2 cell. In system dynamics model, the effects of eight components on the downstream genes of the pathway were simulated by mathematical model.</p><p><strong>Conclusion: </strong>This study indicated that SMB regulated circadian gene expression and improve circadian rhythm disorders. Circadian rhythms were one of important mechanism of action for SMB to exert myocardial injury protective effect.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106782"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FitoterapiaPub Date : 2025-10-01Epub Date: 2025-08-07DOI: 10.1016/j.fitote.2025.106780
Yuliya Prokopenko, Ivan Surzhykov, Olha Golovchenko, Volodymyr Mishchenko, Victoriya Georgiyants
{"title":"Fumaria officinalis: Phytochemical complexity and its medicinal significance.","authors":"Yuliya Prokopenko, Ivan Surzhykov, Olha Golovchenko, Volodymyr Mishchenko, Victoriya Georgiyants","doi":"10.1016/j.fitote.2025.106780","DOIUrl":"10.1016/j.fitote.2025.106780","url":null,"abstract":"<p><p>Fumaria officinalis L. has long been valued in traditional medicine across Europe and Asia, where it has played a significant role in indigenous herbal practices. This review aims to provide a comprehensive examination of the phytochemical composition, pharmacological properties, and potential therapeutic applications of F. officinalis through a modern phytochemistry perspective. Advanced chromatographic and spectroscopic techniques - such as HPLC, GC-MS, and LC-MS/MS - have enabled detailed analysis of its complex chemical profile, with a particular focus on isoquinoline alkaloids and phenolic compounds. Protopine, identified as the predominant alkaloid, together with several phenolic constituents, is implicated in the plant's reported anti-inflammatory, hepatoprotective, and antioxidant activities. A systematic review of literature sourced from major databases including Scopus, PubMed, and ScienceDirect (with an emphasis on studies published within the last decade) was conducted to correlate the chemical composition with pharmacological outcomes. This integration of traditional ethnobotanical knowledge with contemporary analytical methods not only highlights the structural diversity of F. officinalis but also reinforces its potential as a natural source for drug development. The review discusses the quantitative and qualitative aspects of the bioactive compounds, shedding light on their mechanisms of action and potential synergistic effects. Ultimately, these findings support the notion that F. officinalis is a promising candidate for the development of novel natural therapeutics. Further research should prioritize the isolation of additional bioactive constituents, detailed structure elucidation, and clinical validation to fully exploit its pharmacological potential.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106780"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FitoterapiaPub Date : 2025-10-01Epub Date: 2025-08-07DOI: 10.1016/j.fitote.2025.106789
Jong Min Oh, Woong-Hee Shin, Eonmi Kim, Yoon-Ju Kwon, Hoon Kim
{"title":"Potent BACE1 inhibitory and neuroprotective activities of three lignans, styraxlignolide A, masutakeside I, and egonol, isolated from Styrax japonica.","authors":"Jong Min Oh, Woong-Hee Shin, Eonmi Kim, Yoon-Ju Kwon, Hoon Kim","doi":"10.1016/j.fitote.2025.106789","DOIUrl":"10.1016/j.fitote.2025.106789","url":null,"abstract":"<p><p>Intracellular amyloid-β (Aβ) accumulation causes Alzheimer's disease (AD), and thus Aβ-related inhibitors, especially inhibitors of β-secretase 1, known as β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) have been developed to treat AD. The purpose is to evaluate BACE1 inhibitory activity of the compounds isolated from Styrax japonica stem bark, traditionally used as herbal medicines. In this study, seven compounds were isolated, including three lignans, styraxlignolide A, masutakeside I, and egonol. Styraxlignolide A showed potent inhibitory activity against BACE1 with an IC<sub>50</sub> value of 0.173 μM, followed by masutakeside I and egonol (IC<sub>50</sub> = 0.376 and 1.509 μM, respectively), with mixed-type inhibition and low toxicity to normal MDCK and neuroblastoma SH-SY5Y cells. Furthermore, egonol, aglycone of masutakeside I, had neuroprotective activity in SH-SY5Y cells and Aβ<sub>42</sub> aggregation inhibitory activity with blood-brain barrier permeability. The binding energies of styraxlignolide A, masutakeside I, and egonol, for BACE1 were predicted to be -11.753, -11.041, and - 8.413 kcal/mol, respectively. It was found that styraxlignolide A was the most potent BACE1 inhibitor compared with other herbal molecules reported to date. In conclusion, styraxlignolide A, masutakeside I, and egonol are potent mixed-type BACE1 inhibitors, suggesting that they can be used as drug candidates for therapeutic agents of AD.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106789"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FitoterapiaPub Date : 2025-10-01Epub Date: 2025-08-09DOI: 10.1016/j.fitote.2025.106786
Deepak Kumar, Ankit Chaudhary, Choudhury Omm Prakash Kar, Aqib Sarfraz, M Srijeet Kumar Rao, Feroz Khan, Prasant Kumar Rout
{"title":"Synthesis of β-Hydroxy-β-methylglutaryl- coenzyme A reductase inhibitors utilizing in-situ and ex-situ recovered phytosterols from Gymnema sylvestre R. Br. Processing waste.","authors":"Deepak Kumar, Ankit Chaudhary, Choudhury Omm Prakash Kar, Aqib Sarfraz, M Srijeet Kumar Rao, Feroz Khan, Prasant Kumar Rout","doi":"10.1016/j.fitote.2025.106786","DOIUrl":"10.1016/j.fitote.2025.106786","url":null,"abstract":"<p><p>Natural product industries are facing challenge in residual waste disposal. To mitigate this concern, an industrial methodology was established utilizing solid herbal waste (SHW) and phytosterol waste (PW<sub>in</sub>) generated while preparing commercial hypoglycemic extracts from Gymnema sylvestre. Chromatographic evaluation of SHW and PW<sub>in</sub> (HPLC and TLC) discovered them as a potential source of phytosterols. PW<sub>in</sub> (4.63 ± 0.04 % (w/w)) was recovered during initial defatting step (Hexane: Herb, 15:1, 50 °C, 6 h) and after the extraction of Gymnemic acids PW<sub>ex</sub> (4.49 ± 0.13 % (w/w)) was recovered by extracting the SHW with ethyl acetate (ethyl acetate: Herb, 15:1, 50 °C, 6 h). Stigmasterol (I) (most abundant phytosterol) was isolated from PW<sub>in</sub> and PW<sub>ex</sub> on an industrial scale and subjected to stigmasteryl acetates modification. Stigmasterol (1 mM) with respective anhydrides/carbonyl chlorides (1.12 mM) was stirred at 40 °C along with 0.5 mM of DMAP in 20 mL DCM. The synthesized stigmasteryl acetates (II-VI) were performed better with respect to Stigmasterol (I) in In-silico docking analysis. Compound VI was found most affinitive with HMGCoAR, attenuates hypercholesterolemia, and improves blood cholesterol profile of experimental animals when tested In-vivo. Findings suggest that recovery of chemical resources could be valuable in providing sustainable waste utilization approach for natural product industry.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106786"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FitoterapiaPub Date : 2025-09-30DOI: 10.1016/j.fitote.2025.106918
Yongyong Ren , Peilin Wang , Feng Yang , Honglu Xiang , Meng Sun , Kui Hong , Anqi Geng , Jin Li
{"title":"Bioactive components from Kaixin san alleviate bradyarrhythmia via modulation of the calcium signaling pathway: Integrated UPLC-Q-TOF/MS, network pharmacology, and experimental validation","authors":"Yongyong Ren , Peilin Wang , Feng Yang , Honglu Xiang , Meng Sun , Kui Hong , Anqi Geng , Jin Li","doi":"10.1016/j.fitote.2025.106918","DOIUrl":"10.1016/j.fitote.2025.106918","url":null,"abstract":"<div><div>Kaixin San (KXS), a traditional Chinese medicine formula, has shown therapeutic potential in treating bradyarrhythmia (BA), yet its active constituents and pharmacological mechanisms remain insufficiently defined. In this study, an integrated approach combining UPLC-Q-TOF/MS, network pharmacology, molecular docking, and experimental validation was employed to investigate the bioactive compounds and potential mechanisms of KXS. A total of 23 representative compounds were identified, including saponins, flavonoids, phenylpropanoids, organic acids, and lignans. Network pharmacology analysis revealed calcium signaling as a key pathway implicated in the anti-arrhythmic effect of KXS, with CACNA1C and CAMKIIδ predicted as major targets. Molecular docking and dynamics simulation confirmed strong binding affinity between KXS compounds and these core proteins. In a propranolol-induced BA rat model, KXS significantly improved cardiac conduction, modulated heart rate, and attenuated myocardial injury. Further experimental results confirmed that KXS downregulated the expression of CACNA1C and CAMKIIδ in myocardial tissue, suggesting its role in regulating intracellular calcium homeostasis. In conclusion, KXS alleviates bradyarrhythmia in rats, potentially by modulating calcium signaling pathways. This study highlights the multi-component and multi-target nature of KXS and provides a scientific basis for its application in BA treatment.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106918"},"PeriodicalIF":2.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FitoterapiaPub Date : 2025-09-30DOI: 10.1016/j.fitote.2025.106912
Cong Nie , Die Pei , Jieyi Huang , Shanru Chen , Qihui Deng , Keqi Zeng , Xin Zhou , Wanyi Liu , Lixia Zhu , Yingfeng Zhang
{"title":"Combined cell membrane solid-phase chromatography and microdialysis-based metabolomics to explore the material basis of Chaihu Shugan San against post-stroke depression","authors":"Cong Nie , Die Pei , Jieyi Huang , Shanru Chen , Qihui Deng , Keqi Zeng , Xin Zhou , Wanyi Liu , Lixia Zhu , Yingfeng Zhang","doi":"10.1016/j.fitote.2025.106912","DOIUrl":"10.1016/j.fitote.2025.106912","url":null,"abstract":"<div><div>Chaihu Shugan San (CSS) has a good therapeutic effect on post-stroke depression (PSD), but its pharmacodynamic material basis is still unclear. This study revealed the pharmacodynamic material basis of CSS against PSD based on cell membrane solid-phase chromatography and hippocampal metabolomics. Therefore, the specific binding components of CSS and HT22 cells were screened by cell membrane solid-phase chromatography combined with ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) technique, and their effects on the viability and brain-derived neurotrophic factor (BDNF) of injured HT22 cells were evaluated. Conduct metabolomics on the hippocampus of PSD rats with the intervention of CSS combining the brain microdialysis technique and UPLC-Q-TOF-MS, and biological networks were constructed to reveal the mechanism of action of CSS anti-PSD, and molecular docking was performed to evaluate the binding ability of HT22 specific binding components to target proteins. The results showed that 8 specific binding components of CSS and HT22 cells were identified by cell membrane solid-phase chromatography. Except for Nobiletin, the other 7 components could protect HT22 cells and significantly increase BDNF levels. The UPLC-Q-TOF-MS technique identified 13 differential metabolites in metabolomics. Biological network analysis revealed that glutathione metabolism might be an important pathway for CSS anti-PSD. The specific binding component of HT22 was well-bound to the target protein.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106912"},"PeriodicalIF":2.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FitoterapiaPub Date : 2025-09-30DOI: 10.1016/j.fitote.2025.106916
Yalu Mi , Xinyang Tian , Qing Yang , Bo Wang
{"title":"Hedyotis diffusa Willd.-Scutellaria barbata D.Don herb pair induces ferroptosis in gastric cancer by inhibiting the PI3K/AKT/HIF-1α pathway","authors":"Yalu Mi , Xinyang Tian , Qing Yang , Bo Wang","doi":"10.1016/j.fitote.2025.106916","DOIUrl":"10.1016/j.fitote.2025.106916","url":null,"abstract":"<div><div>The herb pair comprising <em>Hedyotis diffusa</em> Willd. and <em>Scutellaria barbata</em> D.Don (HD-SB) is widely utilized in oncological therapies. Nevertheless, the mechanisms underlying its suppressive effects on gastric cancer (GC) remain inadequately elucidated. This investigation aims to delineate the therapeutic efficacy and molecular targets of HD-SB against GC through an integrative approach combining high-performance liquid chromatography-mass spectrometry (HPLC-MS), network pharmacology, molecular docking, and experimental validation. Thirty-three bioactive compounds were retrieved for HD-SB, yielding 288 putative therapeutic targets relevant to GC. Protein-protein interaction (PPI) network analysis highlighted 23 pivotal targets, including AKT1 and HIF-1α. Functional enrichment analyses <em>via</em> Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways indicated significant involvement of the PI3K/AKT signaling cascade and transcription factor activity. Molecular docking studies demonstrated strong binding affinities between principal HD-SB constituents and core targets AKT1 and HIF-1α. Bioinformatic analysis revealed elevated mRNA and protein expression levels of AKT1 and HIF-1α in GC tissues relative to normal gastric tissues, with increased <em>AKT1</em> expression correlating with poorer patient prognosis. <em>In vitro</em> assays confirmed that HD-SB markedly inhibited GC cell proliferation, while <em>in vivo</em> experiments substantiated its antitumor efficacy. Mechanistically, HD-SB was shown to induce ferroptosis in GC cells by suppressing the PI3K/AKT/HIF-1α pathway. Collectively, these findings suggest that HD-SB exerts antineoplastic effects in GC by promoting ferroptosis through modulation of the PI3K/AKT/HIF-1α signaling axis, underscoring its potential clinical utility in GC management.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106916"},"PeriodicalIF":2.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FitoterapiaPub Date : 2025-09-29DOI: 10.1016/j.fitote.2025.106910
Guangyao Li , Jiaxin Yu , Ziqiao Yang , Xiuqiang Xia , Guoying Zhang , Kejian Li , Jianya Ling
{"title":"Mechanistic analysis of Inonotus hispidus in ameliorating T2DM: Metabolomics and gut microbiota profiling in mice models","authors":"Guangyao Li , Jiaxin Yu , Ziqiao Yang , Xiuqiang Xia , Guoying Zhang , Kejian Li , Jianya Ling","doi":"10.1016/j.fitote.2025.106910","DOIUrl":"10.1016/j.fitote.2025.106910","url":null,"abstract":"<div><div>As a large medicinal fungus, <em>Inonotus hispidus</em> (<em>I. hispidus</em>) has multiple pharmacological effects such as antioxidation, anti-inflammation, and hypoglycemia. However, studies on improving type 2 diabetes mellitus (T2DM) by the secondary metabolites of <em>I. hispidus</em> are still insufficient. In this study, we constructed HepG2-IR, HepG2-NAFLD cell models and a high-fat diet combined with streptozotocin-induced T2DM mice model. Using untargeted metabolomics, 16S rRNA gene sequencing of the gut microbiota, and Q Exactive UPLC-MS/MS analysis, we identified the active components of the <em>I. hispidus</em> ethanol extract (IHE) and elucidated its mechanisms against T2DM. The results showed that <em>I. hispidus</em> exerted hypoglycemic and hypolipidemic effects, and significantly reduced the serum levels of TC, TG, AST, and ALT in T2DM model mice. IHE enhanced antioxidant enzyme activities and reduced serum levels of inflammatory cytokines (IL-6, TNF-<em>α</em>). Mechanistically, it inhibited the TNF-<em>α</em>/NF-<em>κ</em>B signaling pathway. Metabolomics combined with 16S amplicon sequencing analysis revealed that <em>I. hispidus</em> can increase the levels of metabolites such as naringenin chalcone and genistein, which have hypoglycemic and anti-inflammatory effects. Furthermore, these differential metabolites were significantly correlated with the increased abundance of <em>Akkermansia</em> and <em>Bacteroides</em>, as well as the decreased abundance of harmful bacterial genera such as <em>Blautia</em> and <em>Desulfovibrio</em>. In addition, 66 compounds were characterized in <em>I. hispidus</em>, with polyphenols being the main chemical constituents exerting therapeutic effects. This study provides an experimental basis for the multi-pathway improvement of T2DM by <em>I. hispidus</em>.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106910"},"PeriodicalIF":2.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}