Pharmacological Research - Natural Products最新文献

{"title":"Macrophages in Inflammation, Insulin Resistance, and Therapeutic Targets: Exploring the Potential of Graptophyllum pictum","authors":"Najib Mohammed ,&nbsp;Fatchiyah Fatchiyah ,&nbsp;Muhammad Sasmito Djati ,&nbsp;Muhaimin Rifa’i ,&nbsp;Sri Rahayu","doi":"10.1016/j.prenap.2025.100344","DOIUrl":"10.1016/j.prenap.2025.100344","url":null,"abstract":"<div><div>Type 2 diabetes has reached epidemic proportions globally, with insulin resistance (IR) serving as a major pathogenic factor that frequently presents alongside obesity. Chronic low-grade inflammation, primarily mediated by macrophages, contributes to IR and T2DM. The urgent need for safer, more targeted, and mechanism-based therapies has driven increasing interest in natural compounds with immunomodulatory effects. This review explores the molecular pathways linking macrophage-driven inflammation to IR, evaluates current therapeutic strategies targeting macrophages and pro-inflammatory cytokines, and examines the potential of <em>Graptophyllum pictum</em> as a natural intervention. <em>G. pictum</em>, rich in flavonoids, phenolics, and other bioactive compounds, exhibits potent anti-inflammatory, antioxidant, and hypoglycemic activities. Its ability to modulate cytokine production and macrophage activity makes it a promising natural agent for mitigating inflammation-induced IR. Given the limitations of current therapies, future studies should aim to isolate key bioactive compounds and conduct clinical trials to demonstrate their efficacy and safety in treating IR and T2DM.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"8 ","pages":"Article 100344"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective effects of a Cassia fistula fruit extract and molecular insights into its phytoconstituents’ interactions with Keap1","authors":"B.M. Faysal Ahmed ,&nbsp;Ariful Islam ,&nbsp;Khayrunnahar ,&nbsp;Muaz Faruque ,&nbsp;Asaduzzaman ,&nbsp;As-Sazzad Mahmud ,&nbsp;Md. Monirul Islam ,&nbsp;Veronique Seidel ,&nbsp;Md Afjalus Siraj","doi":"10.1016/j.prenap.2025.100341","DOIUrl":"10.1016/j.prenap.2025.100341","url":null,"abstract":"<div><div><em>Cassia fistula</em> L. (Fabaceae) is a plant indigenous to Bangladesh, India, Thailand, China and other South Asian countries. It has a long history of use in traditional medicine to treat various ailments including diabetes, skin and liver disorders. This study aimed to investigate the hepatoprotective activity of the ethanolic extract of <em>Cassia fistula</em> (EECF) fruits using a combination of <em>in vivo</em> and <em>in silico</em> analyses. The <em>in vivo</em> hepatoprotective activity was evaluated using an acetaminophen-induced hepatoxicity assay with oral administration of EECF to adult female non-pregnant white Sprague-Dawley albino rats at doses of 250, 500 and 750 mg/kg b.w and subsequent determination of AST, ALT, ALP, bilirubin, TG, TC, HDLc, LDLc, total protein and serum albumin levels. Molecular docking and molecular dynamic simulations were performed using the YASARA software to predict the binding affinities and molecular interactions of selected EECF phytoconstituents towards the target protein Keap1. HPLC analysis of EECF revealed the presence of (+) catechin, (–)-epicatechin, syringic acid and <em>trans</em>-ferulic acid. In the <em>in vivo</em> experiments, EECF showed significant hepatoprotective activity against acetaminophen-induced hepatotoxicity. (+)-Catechin showed a strong binding affinity towards Keap-1, suggesting its potential role in accelerating the Nrf2-Keap1 dissociation and subsequent activation of mechanisms that protect hepatocytes from oxidative stress and promote liver regeneration. Taken altogether these findings provide scientific evidence to justify, to some extent, the traditional use of <em>C. fistula</em> in liver disorders.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"8 ","pages":"Article 100341"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the anti-prostate potentials of n-hexane fraction of berries of Solanum aculeastrum Dunal through in silico and in vitro evaluation","authors":"Gift Crucifix Pender ,&nbsp;Bernard Guyah ,&nbsp;Peter Githaiga Mwitari ,&nbsp;Mercy Jepkorir ,&nbsp;Inyanyi John L. Lagu ,&nbsp;James Ombaka","doi":"10.1016/j.prenap.2025.100336","DOIUrl":"10.1016/j.prenap.2025.100336","url":null,"abstract":"<div><div>The study investigated antiprostatic effects of n-hexane fraction of <em>S. aculeastrum</em> Dunal berries (HFSADB) against benign prostatic hyperplasia (BPH) and prostate cancer (PC). Using Swiss ADME and pKCSM tools, drug candidates were obtained from HFSADB. Using BindingDB, Swiss Target Prediction and DisGeNET databases, compounds, and disease targets for BPH and PC were identified. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to predict mechanisms and pathways of interactions between compounds and target genes, respectively. Molecular docking was done using VINA tool. Antiproliferative activity and gene expression analysis of HFSADB were conducted using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) bioassay and RT-qPCR respectively, and data analyzed using Graph Pad Prism (version 8.4). Three molecules [(-)-cis-.beta.-Elemene; beta-Humulene; and Cadina-1(10),4-diene] were identified as drug candidates. Key targets include NCOA3, ESR2, PPARA, amongst others. GO analysis revealed key targets were mainly enriched in 327 biological processes (BP) terms, 43 molecular function (MF) terms and 5 cellular components (CC) terms (p &lt; 0.05), while KEGG analysis revealed pathways in cancer, PPAR signaling pathway amongst others as primarily associated pathways. Docking analysis revealed two of the compounds [(-)-cis-.beta.-Elemene; and Cadina-1(10),4-diene] demonstrated strong binding affinity with PTGS2 and CYP19A1 target genes. HFSADB significantly (p &lt; 0.0001) inhibited growth of DU-145 cells with IC₅₀ value and selectivity index of 5.478 μg/ml and 10.67, respectively, while sparing Vero CCL-81 cells. Significant (p &lt; 0.0001) downregulation of PTGS2 and BCL-2 were observed in treated DU-145 cells compared to control. HFSADB demonstrated antiprostate activities.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"8 ","pages":"Article 100336"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Gossypium merserverium as an antimalarial agent: In vitro and computational studies","authors":"Enitan Omobolanle Adesanya ,&nbsp;Akingbolabo Daniel Ogunlakin ,&nbsp;Gideon Ampoma Gyebi ,&nbsp;Omobolaji Olumide Odunayo ,&nbsp;Mariam Oyindamola Odunlami ,&nbsp;Adeola Victoria Ogunbowale ,&nbsp;Damilare Ogundare ,&nbsp;Timileyin Odusanya ,&nbsp;Abraham Oluwalana Nkumah","doi":"10.1016/j.prenap.2025.100338","DOIUrl":"10.1016/j.prenap.2025.100338","url":null,"abstract":"<div><div><em>Gossypium merserverium</em> leaves' decoction has traditionally been used in treating malaria, but no scientific data exists. Therefore, this study investigates the antiplasmodial potential of the plant extract from <em>Gossypium merserverium</em>. The methanol extract was obtained through <em>in vacuo</em> concentration of the methanol extract of <em>G. merserverium</em>. Thereafter, the <em>in vitro</em> assay of the extract was tested for its 50 % inhibitory concentration (IC50) using the β-haematin inhibition assay. The Gas Chromatography-Mass Spectrometry (GC-MS) analysis was conducted to identify compounds present in the extract, and identified compounds in <em>G. merserverium</em> were subjected to computational analysis focusing on ICET. Methanolic extract of <em>G. merserverium</em> exhibited an IC₅₀ value of 175.8 ± 0.02 μg/mL. The GC-MS analysis result identified 38 compounds, including Bis(2-ethylhexyl)phthalate, Thymol<strong>,</strong> Neophytadiene<em>,</em> Hexadecanoic acid methyl ester, and Phytol<em>. In silico</em> study on the compounds identified in <em>Gossypium merserverium</em> via GC-MS analysis, the ICET_Bis(2-ethylhexyl)phthalate showed the greatest variability, ranging from 35 to 45 ns. These findings offer a basis for future research into specific compounds responsible for their antiplasmodial properties and the nature of their interaction with chloroquine and other standard antimalarial drugs. This could optimize these extracts for malaria treatment.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"8 ","pages":"Article 100338"},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic and clinical insights into the antidiabetic potential of Cinnamomum cassia: A review","authors":"Ishita Debnath ,&nbsp;Suman Ghosh ,&nbsp;Sobhanjan Bhunia ,&nbsp;Aditi Nayak ,&nbsp;Sumit Nandi ,&nbsp;Soumik Bhattacharjee","doi":"10.1016/j.prenap.2025.100340","DOIUrl":"10.1016/j.prenap.2025.100340","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia, particularly Type 2 Diabetes Mellitus (T2DM), due to defects in insulin secretion, action, or both. Traditional Chinese Medicine (TCM) has long utilized <em>Cinnamomum cassia</em>, known for its potent therapeutic properties in managing various ailments. Modern pharmacological research has begun to validate these traditional uses, focusing on the bioactive compounds within <em>C. cassia</em> that contribute to its hypoglycemic effects.</div></div><div><h3>Objectives</h3><div>This review aims to comprehensively evaluate the mechanistic insights into the role of <em>C. cassia</em> in blood glucose regulation, its phytochemical constituents, and its clinical efficacy in diabetes management. This study integrates traditional knowledge with current researches to enhance <em>C. cassia</em>’s role in diabetes therapy.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted using indexed databases such as Scopus, ScienceDirect, MDPI, PubMed, and Web of Science, based on relevance, focusing on animal, in vitro studies related to <em>C. cassia</em>'s antidiabetic effects, and as a use of TCM.</div></div><div><h3>Results</h3><div><em>Cinnamomum cassia</em> exhibits significant antidiabetic properties primarily through its active compound, cinnamaldehyde. This compound modulates key metabolic pathways, such as PI3K/AKT and AMPK, enhancing insulin sensitivity and glucose uptake. In vitro and in vivo studies have demonstrated the efficacy of <em>C. cassia</em> in improving glycemic control, reducing fasting blood glucose levels, and enhancing β-cell function. Clinical trials corroborate these findings, indicating reduced HbA1c and improved lipid profiles in diabetic patients supplemented with <em>C. cassia</em>. Furthermore, traditional TCM preparations incorporating <em>C. cassia</em> have shown synergistic effects, enhancing the overall therapeutic outcomes.</div></div><div><h3>Conclusion</h3><div><em>Cinnamomum cassia</em> as a potent natural intervention for managing diabetes mellitus, particularly T2DM. Its multifaceted mechanisms in both traditional and modern medicinal practices underscore its potential as a complementary therapy. Future research should refine extraction methods to minimize adverse effects while maximizing therapeutic benefits.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"8 ","pages":"Article 100340"},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Mpox virus proteins with tea phytochemicals: A computational study","authors":"Sumit Arora ,&nbsp;Pranjali Kapgate ,&nbsp;Avanti Girdekar ,&nbsp;Keshav Moharir ,&nbsp;Subhash Yende ,&nbsp;Sapan Shah ,&nbsp;Uday Harle","doi":"10.1016/j.prenap.2025.100337","DOIUrl":"10.1016/j.prenap.2025.100337","url":null,"abstract":"<div><div>The recent Mpox outbreak has highlighted the need for effective antiviral treatments. This study explores the potential of <em>Camellia sinensis</em> phytochemicals as inhibitors of the Mpox virus methyltransferase VP39 using <em>in-silico</em> molecular docking. Twenty-six phytochemicals were docked against the VP39 crystal structure (PDB ID: 8B07) and compared to the native ligand Sinefungin. Myricetin-3-glucoside emerged as the most promising compound with a binding affinity of − 8.5 kcal/mol, forming an extensive hydrogen bonding network and hydrophobic interactions. Structure-activity relationship analysis revealed the importance of hydroxylation patterns and glycosylation in flavonoid binding. Chlorogenic acid (-8.1 kcal/mol) was the top-performing phenolic acid, suggesting the quinic acid moiety's role in complex stabilization. Alkaloids demonstrated weaker binding, while anthocyanins, particularly Petunidin (-8.0 kcal/mol), showed promising results. Key residues involved in ligand binding were identified, including VAL-116, ARG-140, ASP-138, PHE-115, and VAL-139. Drug-likeness and ADME analysis revealed that while some potent binders violated Lipinski's rules, several compounds, including Myricetin, Chlorogenic acid, and Petunidin, combined strong binding with favorable drug-like properties. These findings provide a foundation for the development of <em>Camellia sinensis</em>-derived antiviral agents against Mpox, pending experimental validation.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"8 ","pages":"Article 100337"},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential and pharmaceutical development of multitargeted polyphenolic compound ethyl gallate","authors":"Roshni Sharma ,&nbsp;Mohammad Adnan Raza ,&nbsp;Anjila Firdous ,&nbsp;Ajazuddin","doi":"10.1016/j.prenap.2025.100339","DOIUrl":"10.1016/j.prenap.2025.100339","url":null,"abstract":"<div><div>Ethyl gallate, a derivative of gallic acid, having significant characteristics including anti-inflammatory, antioxidant &amp; antiviral, positioning it as potential candidate for therapeutic applications across several different illnesses, such as inflammatory condition, cancer, and viral illnesses like influenza, herpes simplex. Preclinical studies have shown that it has the capacity to modulate inflammation and oxidative stress, both of them plays significant roles in a variety of pathological diseases. The versatility of ethyl gallate in addressing a lot of disease pathways demonstrates its promise in integrated therapeutic methods. However, despite promising in vitro and animal model results, its clinical use remains unknown. The lack of human clinical studies leaves a significant vacuum in our findings, particularly of its safety, efficacy, and comprehensive pharmacological mechanisms. Future study is required to close this gap and establish the therapeutic value of ethyl gallate.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"8 ","pages":"Article 100339"},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Abelmoschus manihot (L.) Medik chloroform leaf extract on streptozotocin-induced diabetic rats","authors":"Selvaraj Divya ,&nbsp;Subramanian Arivoli ,&nbsp;Samuel Tennyson","doi":"10.1016/j.prenap.2025.100335","DOIUrl":"10.1016/j.prenap.2025.100335","url":null,"abstract":"<div><div>Ethnomedicine is a potentially fruitful area of study in treating diabetes since plants are reported to possess antidiabetic properties. In this study, <em>Abelmoschus manihot</em> leaf chloroform extract (AMLCE) was assessed for its antidiabetic effect on streptozotocin (STZ)-induced diabetic Wistar albino rats. The experimental design comprised of seven groups with six rats in each group, viz., Group I: Normal control, Group II: STZ (Diabetic control), Group III: STZ + AMLCE [100 mg/Kg BW], Group IV: STZ + AMLCE [200 mg/Kg BW], Group V: STZ + AMLCE [400 mg/Kg BW], Group VI: STZ + Glibenclamide [600 µg/Kg BW], and Group VII: Normal control + AMLCE [400 mg/Kg BW]. Body weight of Group I, II and V were 207.23 ± 8.99, 121.98 ± 7.61 and 162.82 ± 7.18 g, respectively; and their respective plasma glucose levels were 95.31 ± 4.53, 286.93 ± 4.82 and 126.88 ± 7.14 mg/dL. The insulin and total haemoglobin levels of Group I, II and V were 16.62 ± 1.10, 7.20 ± 2.60, 11.90 ± 1.72 µU/mL; and 12.60 ± 1.68, 6.51 ± 0.62, 10.17 ± 0.54 g/dL, respectively. When compared to the STZ-induced diabetic Wistar albino rats, AMLCE significantly increased the body weight and levels of insulin levels and total haemoglobin (<em>P≤</em>0.05) and decreased plasma glucose level (<em>P≤</em>0.05). AMLCE Group V was taken up for further studies since it showed a noteworthy impact in comparison to the other two groups of AMLCE. The histopathological study revealed STZ-induced diabetic Wistar albino rats treated with AMLCE with restoration of β-cells in islet of Langerhans in pancreas, regeneration of hepatocytes in liver, and restoration of glomerulus tubules in kidney. The expression of IR, PI3K, p-Akt, and GLUT-2 protein levels in STZ-induced diabetic Wistar albino rats increased upon treatment with AMLCE. The findings of this investigation suggest that AMLCE exhibited anti-diabetic effect. This study represents the first report on the anti-diabetic effects of AMLCE on STZ-induced diabetic Wistar albino rats.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"8 ","pages":"Article 100335"},"PeriodicalIF":0.0,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A glance on the anticancer activities of natural products from marine derived fungi, Aspergillus sp.","authors":"Gulab Said","doi":"10.1016/j.prenap.2025.100334","DOIUrl":"10.1016/j.prenap.2025.100334","url":null,"abstract":"<div><div>Marine derived fungi are rich sources of bioactive compounds. Among them, <em>Aspergillus</em> sp. are promising producers of marine bioactive compounds. The present review provides an overview of anticancer natural products that are produced by marine derived fungi <em>Aspergillus</em> sp. and the derivatives of some of them, covering the literature from 1997 to 2025. Subsequently, 185 natural products and their derivatives that have a broad range of potent anticancer activities against various cancer cell lines are stated in this review. Consequently, it is found that secondary metabolites derived from marine <em>Aspergillus</em> sp., showed a promising avenue for cancer treatment and offering unique mechanisms of action as well as potential advantages over the traditional chemotherapeutic agents.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"8 ","pages":"Article 100334"},"PeriodicalIF":0.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of linalyl acetate, (-)-menthone, and myrtenol against bacterial strains carrying efflux pumps and toxicity against Drosophila melanogaster","authors":"Maria Jéssica Mendes Brito ,&nbsp;Cícera Datiane de Morais Oliveira Tintino ,&nbsp;Isaac Moura Araújo ,&nbsp;Raimundo Luíz Silva Pereira ,&nbsp;Alisson Justino Alves da Silva ,&nbsp;Ana Carolina Justino de Araújo ,&nbsp;Francisco Assis Bezerra da Cunha ,&nbsp;Zildene de Sousa Silveira ,&nbsp;Nair Silva Macedo ,&nbsp;Gildênia Alves de Araújo ,&nbsp;José Maria Barbosa Filho ,&nbsp;Francisco Roberto de Azevedo ,&nbsp;Samara Alves Brito ,&nbsp;Rayane de Tasso Moreira Ribeiro ,&nbsp;Saulo Relison Tintino","doi":"10.1016/j.prenap.2025.100330","DOIUrl":"10.1016/j.prenap.2025.100330","url":null,"abstract":"<div><div>This study aimed to evaluate the antibacterial activity of the monoterpenes linalyl acetate, (-)-menthone, and myrtenol against two bacterial strains with efflux pump mechanisms, namely <em>Staphylococcus aureus</em> 1199B and K2068, which carry the efflux pumps NorA and MepA, respectively. Additionally, the toxicity of these monoterpenes was assessed in the arthropod model <em>Drosophila melanogaster</em>. The broth microdilution method was used to perform Minimum Inhibitory Concentration (MIC) tests at subinhibitory concentrations (MIC/8) in combination with norfloxacin, ciprofloxacin, and ethidium bromide to evaluate their combined effects. Toxicity evaluation of linalyl acetate, (-)-menthone, and myrtenol on <em>D. melanogaster</em> was conducted using fumigation bioassays and negative geotaxis methods. The results were expressed as the mean of triplicate replicates. Two-Way ANOVA followed by Bonferroni's post hoc test was used for statistical analysis. The present study demonstrated that linalyl acetate, (-)-menthone, and myrtenol did not exhibit direct antibacterial activity against the SA-1199B and SA-K2068 strains, as their MIC was ≥ 1024 μg/mL. When combined with norfloxacin, none of the compounds reduced the antibiotic's MIC, and when combined with ethidium bromide, only myrtenol reduced the MIC. For the SA-K2068 strain carrying the MepA efflux pump, all compounds reduced the MIC when combined with ciprofloxacin, and only myrtenol reduced the MIC of ethidium bromide. These results suggest that myrtenol may act as an efflux pump inhibitor for both NorA and MepA. Regarding the toxicity test with <em>D. melanogaster</em>, (-)-menthone exhibited the highest mortality rate. Myrtenol and (-)-menthone showed a greater interference with the animals' flight performance.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"8 ","pages":"Article 100330"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}