Fitoterapia最新文献

{"title":"Alkaloids with cytotoxic activities from Zanthoxylum nitidum","authors":"Wei Wei ,&nbsp;Jing-Hui Yin ,&nbsp;Bang-Yong Wang ,&nbsp;Lin-Lin Luo ,&nbsp;Xiao-Xiao Mo ,&nbsp;Qin-Gang Tan","doi":"10.1016/j.fitote.2025.106913","DOIUrl":"10.1016/j.fitote.2025.106913","url":null,"abstract":"<div><div>Two previously undescribed alkaloids, 8-<em>O</em>-demethylmaclekarpine D (<strong>1</strong>) and zanthonitine (<strong>2</strong>), along with a pair of inseparable rotamers, 4-hydroxyl-beecheyamide (<strong>3a</strong>) and (<em>E</em>)-3-(4-hydroxy-3-methoxyphenyl)-<em>N</em>-(4-methoxyphenethyl)-<em>N-</em>methylacrylamide (<strong>3b</strong>), were isolated from <em>Zanthoxylum nitidum</em>. These compounds were accompanied by 35 known alkaloids, including benzophenanthridines (<strong>4–21</strong>), quinolines (<strong>22</strong>−<strong>31</strong>), aporphines (<strong>32</strong>–<strong>35</strong>) and other structural types (<strong>36–38</strong>). Structural elucidation was achieved through comprehensive spectroscopic analyses, including NMR, HRESIMS, X-ray crystallography, ECD and calculated ¹³C NMR DP4+ analysis. Cytotoxicity evaluation revealed compounds <strong>6</strong>, <strong>7</strong>, <strong>18</strong> and <strong>33</strong> (IC₅₀ = 7.29–22.90 μM) exhibited potent inhibitory effects on the proliferation of HepG2 cells, outperforming the efficacy of doxorubicin (IC₅₀ = 28.92 ± 0.48 μM). Similarly, compounds <strong>9</strong>, <strong>16</strong> and <strong>21</strong> (IC₅₀ = 21.77–25.13 μM) suppressed SW480 cells, superior to doxorubicin (IC₅₀ = 31.15 ± 0.24 μM).</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106913"},"PeriodicalIF":2.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206103","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":"In silico structure revision of zerumol A","authors":"Mikhail E. Elyashberg ,&nbsp;Andrei G. Kutateladze ,&nbsp;Roderick W. Bates ,&nbsp;Craig M. Williams","doi":"10.1016/j.fitote.2025.106914","DOIUrl":"10.1016/j.fitote.2025.106914","url":null,"abstract":"<div><div>The structure of the recently reported natural product, zerumol A, which was proposed to contain an oxetane moiety, was reassigned to a structure containing a 5,6-dihydro-2<em>H</em>-pyran unit. The structure revision was performed using computer assisted structure elucidation (CASE) in combination with DFT approximation DU8ML.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106914"},"PeriodicalIF":2.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206096","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":"Design, synthesis and evaluation of novel 1,3-benzodioxole derivatives for their anti-tumor activity","authors":"Xiu-Jun Wang ,&nbsp;Bing-Yan Wang ,&nbsp;Boyu Zhang ,&nbsp;Lu Chen ,&nbsp;Kuang-Qi Li ,&nbsp;Meng-Meng Wang ,&nbsp;Hui-Hui Hao ,&nbsp;Meng-Xi Lu ,&nbsp;Xing-Xing Shen ,&nbsp;Yu-Kai Sun ,&nbsp;Zhi-Dong Gao ,&nbsp;Zong-Yuan Yan ,&nbsp;Zi-Yan Lang ,&nbsp;Miao-jia-hao Yu ,&nbsp;Zhi-Jun He ,&nbsp;Shao-Jie Ma ,&nbsp;Jing Ji ,&nbsp;Yong-Li Chang","doi":"10.1016/j.fitote.2025.106911","DOIUrl":"10.1016/j.fitote.2025.106911","url":null,"abstract":"<div><div>This study designed novel 1,3-benzodioxole derivatives (a core moiety of piperine essential for activity) by: 1) Retaining the 1,3-benzodioxole ring (critical for antitumor efficacy); 2) Introducing a vinyl linker (enhanced activity vs. direct amide attachment, per our prior work); 3) Incorporating trifluoromethylpiperazine (proven to boost antitumor effects). Target compounds were synthesized via bromination, nucleophilic substitution, reduction, and condensation, with structures confirmed by ¹H NMR, ¹³C NMR, and HR-MS.</div><div>Target compounds were synthesized via bromination, nucleophilic substitution, reduction, and condensation, with structures confirmed by ¹H NMR, ¹³C NMR, and HR-MS. MTT assay showed most derivatives exhibited significant cytotoxicity against HeLa, A498, and MDA-MB-231 cells. Among them, (E)-3-(benzo[d][1,3]dioxol-5-yl)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)acrylamide (YL201) had the strongest activity against MDA-MB-231 cells (IC₅₀ = 4.92 ± 1.09 μM), outperforming 5-fluorouracil (5-Fu, IC₅₀ = 18.06 ± 2.33 μM).</div><div>In vitro assays (colony formation, adhesion, Transwell invasion, wound healing) demonstrated YL201 concentration-dependently suppressed MDA-MB-231 cell proliferation, adhesion, invasion, and migration (e.g., 8 μM YL201 led to 23.30 ± 1.20 % proliferation rate vs. 69.63 ± 3.63 % for 5-Fu). In chick embryo chorioallantoic membrane (CAM) xenografts, YL201 inhibited tumor angiogenesis and reduced tumor weight (8.17 ± 1.17 mg at 8 μM vs. 14.40 ± 1.05 mg for 5-Fu) without affecting chick embryo weight, indicating good in vivo safety.</div><div>SwissADME prediction showed YL201 complies with Lipinski's Rule of Five (MW = 461.48, logP = 3.94, HBA = 8, HBD = 1, rotatable bonds = 8), suggesting favorable druggability. In conclusion, YL201 is a promising candidate for breast cancer treatment worthy of further preclinical research.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106911"},"PeriodicalIF":2.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206060","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":"Chemical and pharmacological richness of Turraeanthus (Meliaceae): A review on progress and future research opportunities","authors":"Guy Paulin M. Kemayou ,&nbsp;Gesquière Laure M. Tiani ,&nbsp;Gervais M. Happi ,&nbsp;Laurice Bracine N. Chenda ,&nbsp;Wei Wang ,&nbsp;Simeon F. Kouam","doi":"10.1016/j.fitote.2025.106915","DOIUrl":"10.1016/j.fitote.2025.106915","url":null,"abstract":"<div><div><em>Turraeanthus</em> (Meliaceae) is a genus of trees and shrubs that is widely distributed across tropical and subtropical regions of Africa. Ethnopharmacological studies of this genus suggest that <em>T. africanus</em> is the species most commonly used in traditional medicine to treat various diseases, including malaria, typhoid fever, stomach aches, intestinal worms, coughs and inflammatory and cardiovascular conditions. Previous chemical studies have identified approximately 86 distinct compounds (including 21 synthetic derivatives), with diterpenoids (40.69 %) representing the predominant chemotaxonomic markers in the <em>Turraeanthus</em> genus. Other reported classes of compounds include limonoids (2.32 %), protolimonoids (16.28 %), triterpenoids (3.48 %), sesquiterpenoids (4.65 %), steroids (8.14 %), epoxyquinols (8.14 %), alkaloids (5.81 %), coumarins (4.65 %) and miscellaneous compounds (5.84 %). Some of these isolates have exhibited various bioactivities, including antibacterial, antifungal, toxic, cytotoxic, antiplasmodial and antioxidant effects. This review compiles insights into the traditional uses and chemical and pharmacological aspects of the <em>Turraeanthus</em> genus from 1965 to May 2025. Additionally, it provides a database for UPLC/MSⁿ studies, as well as evidence on the absorption and permeation properties of the isolated compounds from the genus. The data presented were gathered from scientific articles available in online libraries, including Google Scholar, PubMed, Elsevier and SciFinder. The aim of this work is to inspire further research into the rich chemical diversity of <em>Turraeanthus</em> and potentially contribute to the discovery of new therapeutic agents to improve human health.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106915"},"PeriodicalIF":2.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206052","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":"Discovery of anti-inflammatory phytoconstituents from Lactuca indica L. based on its traditional uses","authors":"Thong Cao-Ly-Tan ,&nbsp;Thai Nguyen-Minh ,&nbsp;Cuong Ngo-Van ,&nbsp;Chen Tran-Van ,&nbsp;Tu Vo-Linh ,&nbsp;Triet Nguyen-Thanh","doi":"10.1016/j.fitote.2025.106902","DOIUrl":"10.1016/j.fitote.2025.106902","url":null,"abstract":"<div><div>The arial parts of <em>Lactuca indica</em> have been traditionally used to relieve skin inflammation or to alleviate stomach-ache. This study aims to evaluate pharmacological activities relating to traditional usage of the plant, with a special focus on anti-inflammatory, anti-bacterial and cytotoxic effects of extracts, followed by bio-activity-guided isolation of phytochemicals. The ethanolic extract was prepared by means of percolation, from which 5 sub-extracts were obtained by sequential liquid-liquid partition, including <em>n</em>-hexane, chloroform, ethyl acetate, <em>n</em>-butanol and aqueous sub-extracts. Through preliminary screening, the <em>n</em>-hexane, chloroform and ethyl acetate sub-extracts showed noteworthy inhibition on NO excessive synthesis in LPS-stimulated RAW 264.7 cells. Only the <em>n</em>-hexane sub-extract demonstrated anti-bacterial effect. None of the sub-extracts expressed cytotoxic effects on human acute leukemia (HL-60), hepatocellular (Hep-G2) or gastric (MKN-7) carcinoma cell lines. Phytochemical investigations of anti-inflammatory constituents were carried out for <em>n</em>-hexane, chloroform and ethyl acetate sub-extracts, leading to isolation of 12 compounds: stearic acid (<strong>1</strong>), glyceryl monostearate (<strong>2</strong>), <em>β</em>-amyrin acetate (<strong>3</strong>), oleanolic acid (<strong>4</strong>), lupeol (<strong>5</strong>), 4<em>α</em>(15),11<em>β</em>(13)-tetrahydroridentin B (<strong>6</strong>), 5-hydroxymethylfurfural (<strong>7</strong>), <em>p</em>-hydroxymethylbenzoic acid (<strong>8</strong>), protocatechuic acid (<strong>9</strong>), succinic acid (<strong>10</strong>), cynaroside (<strong>11</strong>) and lynarin (<strong>12</strong>). Molecular docking was then performed to investigate the underlying mechanism, revealing that four compounds <strong>3</strong>, <strong>4</strong>, <strong>11</strong>, <strong>12</strong> exhibited excellent binding affinities to the iNOS enzyme. This study suggests that <em>L. indica</em> may be the source of promising phytochemicals against inflammation mediated by excessive production of NO. This could be a mechanism contributing to partly explain for traditional applications of this herb.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106902"},"PeriodicalIF":2.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191529","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":"Four new piperidine amide alkaloids from Piper longum fruits and their anti-inflammatory activities","authors":"Ting Li ,&nbsp;Xin-yuan Yu ,&nbsp;Xin-yi Chen ,&nbsp;Si-ying Zeng ,&nbsp;Xiao-chun Zeng ,&nbsp;Liang Cao ,&nbsp;Hai-bo Li ,&nbsp;Yang Yu","doi":"10.1016/j.fitote.2025.106899","DOIUrl":"10.1016/j.fitote.2025.106899","url":null,"abstract":"<div><div><em>Piper longum</em> L., a widely recognized Chinese traditional spice, is extensively used as dietary flavoring agent in Southeast Asia due to its unique taste. As a dual-purpose resource for both food and medicine, the fruits of <em>P. longum</em> have garnered significant attention for their diverse chemical constituents and notable physiological activities. In this study, the phytochemical investigation of the fruits of <em>P. longum</em> resulted in the isolation and identification of 20 structurally diverse piperidine amide alkaloids, including 4 new (<strong>1a/1b</strong>-<strong>4a/b</strong>) and 16 known analogues (<strong>5</strong>–<strong>20</strong>). The enantiomeric mixture of <strong>1a</strong>/<strong>1b</strong> was successfully separated using a chiral column with acetonitrile-water as eluents, while chiral HPLC analysis confirmed that <strong>4</strong> existed as an enantiomeric mixture (<strong>4a</strong>/<strong>4b</strong>) without achieving separation. Their structures were elucidated through comprehensive spectroscopic data analysis (NMR, HRESIMS, IR, UV), electronic circular dichroism (ECD) and by comparison with literature data. Biological evaluations revealed that compounds <strong>2</strong>, <strong>3</strong>, <strong>16</strong>, and <strong>17</strong> exhibited significant inhibitory effects on NO secretion in LPS-stimulated RAW264.7 cells, with IC₅₀ values ranging from 9.9 to 15.76 μM, which were better than hydrocortisone (IC₅₀ = 34.26 ± 2.20 μM). Furthermore, Western blot and real-time PCR assays demonstrated that <strong>2</strong> and <strong>17</strong> markedly downregulated the mRNA levels and the protein expression of iNOS. Notably, <strong>17</strong> partially inhibited the phosphorylation of p65 and reduced the protein expression of TLR4. Thus, the discovery of structurally diverse anti-inflammatory piperidine amide alkaloids from the fruits of <em>P. longum</em> in this study could benefit the further development and utilization of this plant.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106899"},"PeriodicalIF":2.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185070","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":"Virginianoside A, a new steroidal alkaloid saponin from Solanum virginianum: Isolation, structure elucidation and anti-adipogenic activity","authors":"Anuradha Vishwakarma ,&nbsp;Jay Gupta ,&nbsp;Astha Singh ,&nbsp;Anil Nilkanth Gaikwad ,&nbsp;Koneni V. Sashidhara","doi":"10.1016/j.fitote.2025.106897","DOIUrl":"10.1016/j.fitote.2025.106897","url":null,"abstract":"<div><div>A previously unreported 16<em>β</em>-H spirosolane saponin, virginianoside A (<strong>1</strong>), along with three known compounds; diosgenin (2), solasodine (3) and prosapogenin B (4) were isolated from the whole plant of <em>Solanum virginianum</em>. The rare 16<em>β</em>-H configuration of <strong>1</strong> was established through detailed ROESY and HMBC analysis. All compounds were evaluated for anti-adipogenic activity, with <strong>1</strong> and 2 showing significant reduction in lipid accumulation on 3T3-L1 cell line. Virginianoside A (<strong>1</strong>) was the most potent, exhibiting dose-dependent activity, suppressing the expression of PPARγ, C/EBPα, FASN and FABP4, without notable cytotoxicity indicating its action during the early phase of adipocyte differentiation.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106897"},"PeriodicalIF":2.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174439","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":"Synergistic effect of plant-derived deglucoruscin in combination with conventional antimicrobials against Staphylococcus aureus and Candida albicans","authors":"Carmen Festa ,&nbsp;Claudia Finamore ,&nbsp;Mattia Cammarota ,&nbsp;Elisabetta Panza ,&nbsp;Silvia Marchianò ,&nbsp;Stefano Fiorucci ,&nbsp;Angela Zampella ,&nbsp;Elisabetta Buommino ,&nbsp;Simona De Marino","doi":"10.1016/j.fitote.2025.106895","DOIUrl":"10.1016/j.fitote.2025.106895","url":null,"abstract":"<div><div>A detailed phytochemical investigation of rhizomes and roots of <em>Ruscus aculeatus</em> led to the isolation of fifteen pure compounds, belonging to the furostanol and spirostanol glycoside classes<strong>.</strong> Among them, one novel furostanol saponin (<strong>1</strong>) was identified, alongside twelve known furostanol (<strong>2</strong>–<strong>8</strong>) and spirostanol (<strong>11</strong>–<strong>15</strong>) saponins and two sulphated glycosides (<strong>9</strong>–<strong>10</strong>). Structural elucidation of all isolated compounds was accomplished through comprehensive 1D and 2D NMR spectroscopic analyses, complemented by mass spectrometry. The CHCl₃ extract of <em>Ruscus aculeatus</em> and its major metabolite, the spirostanol derivative (<strong>12</strong>), exhibited a weak antimicrobial activity. Of particular interest, compound <strong>12</strong> when co-administered with voriconazole (VOR) showed a significant inhibitory effect against the azole-resistant <em>Candida albicans</em> ATCC 10231 strain, demonstrating a synergistic effect that underscores its potential to restore antifungal efficacy and combat resistance mechanisms.</div><div>These findings highlight compound <strong>12</strong> as a promising adjuvant candidate in antifungal therapy, particularly against resistant <em>Candida</em> strains.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106895"},"PeriodicalIF":2.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174383","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":"PI3K-inhibitory new anthraquinone-xanthone heterodimers from a deep-sea Epichloe sp. SCSIO 41042","authors":"Ying-Ying Song ,&nbsp;Xiao-Yan Pang ,&nbsp;De-Hua Yang ,&nbsp;Cheng-Hai Gao ,&nbsp;Jun-Feng Wang ,&nbsp;Yong-Hong Liu","doi":"10.1016/j.fitote.2025.106893","DOIUrl":"10.1016/j.fitote.2025.106893","url":null,"abstract":"<div><div>Two new xanthone-anthraquinone heterodimers (<strong>1</strong> and <strong>2</strong>), and eleven known anthraquinones (<strong>3</strong>−<strong>13</strong>) were isolated from the deep-sea derived <em>Epichloe</em> sp. SCSIO 41042 fermented on rice medium. Structurally, compounds <strong>1</strong>–<strong>5</strong> feature a unique bicyclo[3.2.2]nonane core formed through dual C<img>C linkages. Their structures and absolute configurations were determined by spectroscopic analyses and calculated electronic circular dichroism (ECD). Molecular docking was performed to characterize the affinity of anthraquinones for phosphatidylinositol 3-kinase (PI3K), identifying those with significant anti-PI3K activity. Active compounds were subsequently profiled via homogeneous time-resolved fluorescence (HTRF) assay for PI3K inhibition, followed by binding affinity validation using surface plasmon resonance (SPR). Activity assay revealed that <strong>2</strong> significantly inhibited both PI3K<em>α</em>^WT and PI3K<em>α</em>^H1047R enzymes, with IC₅₀ values of 2.00 and 3.42 μM, respectively. Further SPR analysis demonstrated a moderate binding affinity between <strong>2</strong> and PI3K, with a <em>K</em>_D of 12.7 μM.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106893"},"PeriodicalIF":2.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174397","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":"Artemisia annua L. extract alleviates glucocorticoid-induced osteoporosis by stimulating bone formation via PGC-1α/Nrf2/HO-1/SOD2 pathway","authors":"Liyong Lai ,&nbsp;Kun Li ,&nbsp;Luying Ding ,&nbsp;Ruiqing Zhu ,&nbsp;Yiping Jiang ,&nbsp;Tianshuang Xia ,&nbsp;Xiaoqiang Yue ,&nbsp;Hailiang Xin","doi":"10.1016/j.fitote.2025.106892","DOIUrl":"10.1016/j.fitote.2025.106892","url":null,"abstract":"<div><div>Oxidative stress (OS) inhibits bone formation and contributes to bone loss in glucocorticoid-induced osteoporosis (GIOP). <em>Artemisia annua</em> L. (AA), an oxidative Chinese medicinal herb traditionally used to treat bone steaming and orthopedic diseases, has shown potential as an anti-osteoporotic agent. In this study, AA extract (AE) was administered to dexamethasone (Dex)-induced GIOP mice to investigate its anti-osteoporotic activity. AE effectively ameliorated bone loss, stimulated bone formation, and mitigated oxidative damage in GIOP mice. In MC3T3-E1 osteoblastic cells, AE rescued the Dex-impaired proliferation and osteogenic differentiation. AE also inhibited the accumulation of ROS and MDA, promoted the activity of CAT and SOD, and upregulated the <strong>expression</strong> of PGC-1α, Nrf2, HO-1, and SOD2. siRNA-mediated knockdown of PGC-1α or Nrf2 counteracted AE's regulatory effects on these antioxidant genes, concomitant with increased oxidative damage in transfected cells. An integrated analysis of virtual pharmacokinetic predictions, authentic pharmacokinetic data, and reported pharmacological effects suggested that luteolin was the principal contributor to the antioxidant and anti-osteoporotic activities of AE. In summary, AE promotes bone formation by improving Dex-injured osteoblast differentiation via the PGC-1α/Nrf2/HO-1/SOD2 pathway, indicating its potential as a therapeutic agent for GIOP and other OS-related orthopedic diseases.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106892"},"PeriodicalIF":2.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174445","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}