Journal of Natural Medicines最新文献

{"title":"Three Kampo medicines—bofutsushosan, boiogito, and daisaikoto—have different effects on host fat accumulation and the intestinal microbiota in a high-fat-diet–induced mouse model of obesity","authors":"Kosuke Nakamichi,&nbsp;Tetsuhiro Yoshino,&nbsp;Masahiro Akiyama,&nbsp;Aya Jibiki,&nbsp;Yuta Yokoyama,&nbsp;Hitoshi Kawazoe,&nbsp;Sayo Suzuki,&nbsp;Kenji Watanabe,&nbsp;Yun-Gi Kim,&nbsp;Tomonori Nakamura","doi":"10.1007/s11418-025-01917-3","DOIUrl":"10.1007/s11418-025-01917-3","url":null,"abstract":"<div><p>Inhibiting body fat accumulation is important for the prevention of obesity. In Japan, three Kampo medicines are commonly used to treat obesity: bofutsushosan, boiogito, and daisaikoto. To compare the influences of these Kampo medicines on the intestinal microbiota, it is necessary to conduct a simultaneous investigation using the same mouse model under the same experimental conditions. C57BL/6J mice were divided into five groups: normal chow (NC), high-fat diet (HFD), HFD + 3% bofutsushosan extract (BTS), HFD + 3% boiogito extract (BOT), and HFD + 3% daisaikoto extract (DST). Epididymal white adipose tissue (WAT) weight, mesenteric WAT weight, serum triglyceride levels, and serum total cholesterol levels were measured. Additionally, total bacteria, alpha diversity, beta diversity, and bacterial composition in stool samples were measured. Body weight and epididymal WAT weight gain were significantly inhibited in the BTS-treated group and DST-treated group, but not in the BOT-treated group, compared with the HFD control group. Additionally, serum total cholesterol levels were significantly lower in the DST-treated group than in the HFD group. Specific intestinal bacteria, <i>Clostridium </i><i>sensu stricto</i><i> 1</i>, <i>Erysipelatoclostridium</i>, <i>Roseburia</i>, and the Lachnospiraceae NK4A136 group, were significantly changed in the Kampo-treated groups compared with the HFD group, and each of them was correlated with body weight gain, body fat rate, epididymal WAT weight, or mesenteric WAT weight. Our simultaneous investigation of BTS, BOT, and DST under the same conditions clearly demonstrated different changes in the intestinal microbiota and different effects on fat accumulation as well as their association among the three Kampo medicines.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"1044 - 1056"},"PeriodicalIF":2.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493340","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":"Correction: Ellagic acid prevents ovariectomy-induced bone loss and attenuates oxidative damage of osteoblasts by activating SIRT1","authors":"Liwei Guo,&nbsp;Pengcheng Wei,&nbsp;Shijie Li,&nbsp;Lulu Zhou,&nbsp;Yunjie Yan,&nbsp;Duan Li","doi":"10.1007/s11418-025-01915-5","DOIUrl":"10.1007/s11418-025-01915-5","url":null,"abstract":"","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"1262 - 1263"},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482807","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 pleiotropic anti-cancer, antiviral, and anti-neuro-immunomodulatory role of methanolic neem bark extract","authors":"Debina Bhattacharyya,&nbsp;Jayasri Das Sarma","doi":"10.1007/s11418-025-01924-4","DOIUrl":"10.1007/s11418-025-01924-4","url":null,"abstract":"<div><p>The miraculous golden tree of the century, neem or <i>Azadirachta indica,</i> has been used in ancient ayurvedic and traditional medicine since the inception of medicinal practices. The phytochemicals present in each part of this tree are known to possess the ability to cure a variety of diseases, from viral, bacterial, and fungal infections and associated pathogenesis to inflammatory diseases, different metabolic disorders, and cancers. Predominant phytochemicals from neem, azadirachtin, nimbin, nimbolide, quercetin, etc., are known to be potent anti-inflammatory, antiviral, and anti-cancer agents. These and many other bio-active compounds from neem restrict the viral spread and replication of β-coronaviruses, Human Immunodeficiency Virus, Herpes Simplex Virus, etc. Likewise, neem extracts and bio-active compounds from neem have been targeting cancer cells by restricting their proliferation, survival, and migration and inducing apoptosis, leading to the establishment of neem as a potent anti-cancer agent. Multiple studies have reported neem's efficiency in intervening with inflammatory pathways and oxidative stress pathways, which are known to be linked to viral infections and cancers. In this review, we discuss the role of methanolic neem bark extracts and their bio-active compounds in preventing β-coronavirus mouse hepatitis virus and SARS-CoV-2 replication and spread, and simultaneously the anti-cancer effects exerted by MNBE via activating pro-apoptotic markers, restricting the proliferation and migration of cervical cancer cells, inducing cell cycle arrest.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"951 - 966"},"PeriodicalIF":2.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324107","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":"Correction: Exploring new natural products by utilizing untapped secondary metabolic pathways in actinomycetes","authors":"Shotaro Hoshino","doi":"10.1007/s11418-025-01922-6","DOIUrl":"10.1007/s11418-025-01922-6","url":null,"abstract":"","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 4","pages":"950 - 950"},"PeriodicalIF":2.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of acetophenone dimers from Acronychia pedunculata on human neuroblastoma SH-SY5Y cells in glutamate-induced apoptosis","authors":"Panuwat Worasrihirun,&nbsp;Ardiansah Ardiansah,&nbsp;Kiminori Matsubara,&nbsp;Khanitha Pudhom","doi":"10.1007/s11418-025-01920-8","DOIUrl":"10.1007/s11418-025-01920-8","url":null,"abstract":"<div><p>Excessive glutamate in the central nervous system is a key pathogenic mechanism in neurodegenerative disorder. This study investigated the neuroprotective effect of acrovestone (AVT), an acetophenone dimer from <i>Acronychia pedunculata,</i> and its underlying mechanism in glutamate-induced neuroblastoma SH-SY5Y cells. The protective effect of AVT was evaluted through cell viability assay and analysis of apoptosis-related protein expression via Western blot analysis. Our finding revealed that AVT significantly improved cell viability under glutamate induced excitotoxicity conditions. Mechanistic investigations demonstrated that AVT attenuated the activation of pro-apoptotic proteins including ERK1/2, Bim, BAX, caspase-3, caspase-7, and caspase-9. Concurrently, AVT upregulated the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Furthermore, AVT modulated the Akt/FoxO3a signaling pathway, alleviating acute oxidative stress caused by glutamate exposure in SH-SY5Y cells. These results suggest that AVT inhibits glutamate-induced neurotoxicity by modulating apoptosis signaling pathway, highlighting its potential as a therapeutic candidate for preventing neurodegenerative diseases.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 4","pages":"938 - 949"},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197986","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":"Eight new resin glycosides, calyhedins XXIV–XXXI, from the rhizomes of Calystegia hederacea","authors":"Masateru Ono,&nbsp;Yosuke Matsuoka,&nbsp;Ryota Arakawa,&nbsp;Hiroyuki Shimadzu,&nbsp;Takumi Nagasawa,&nbsp;Hirotaka Nishikawa,&nbsp;Shin Yasuda,&nbsp;Hiroyuki Miyashita,&nbsp;Kazumi Yokomizo,&nbsp;Hitoshi Yoshimitsu,&nbsp;Ryota Tsuchihasi,&nbsp;Masafumi Okawa,&nbsp;Junei Kinjo","doi":"10.1007/s11418-025-01919-1","DOIUrl":"10.1007/s11418-025-01919-1","url":null,"abstract":"<p>Eight new resin glycosides, named calyhedins XXIV (<b>1</b>)–XXXI (<b>8</b>), were isolated from the rhizomes of <i>Calystegia hederacea</i> Wall. (Convolvulaceae), along with six known calyhedins: calyhedins II (<b>9</b>), III (<b>10</b>), IV (<b>11</b>), V (<b>12</b>), VIII (<b>13</b>), and XII (<b>14</b>). Their structures were determined from the spectroscopic data. Compounds <b>1</b>–<b>7</b> were hexa- or hepta-glycosides with macrolactone structures (jalapins), and their sugar moieties were partially acylated by five organic acids, including 2<i>S</i>-methylbutyric, (<i>E</i>)-2-methylbut-2-enoic, and 2<i>R</i>-methyl-3<i>R</i>-hydroxybutyric acids. Compounds <b>1</b>–<b>7</b> were macrolactones with 22- (<b>1</b>, <b>7</b>), 23- (<b>2</b>), 27- (<b>3</b>–<b>5</b>), or 28- (<b>6</b>) membered rings. Compound <b>8</b> was identified as an acylated glycosidic acid methyl ester, corresponding to the compound in which the lactone ring of <b>1</b> was cleaved and subsequently methylated. In addition, the cytotoxic activities of <b>1</b>–<b>8</b>, <b>11</b>, <b>12</b>, and <b>14</b> against HL-60 human promyelocytic leukemia cells and the antiviral activities of <b>1</b>–<b>14</b> and 11 previously isolated calyhedins against herpes simplex virus type 1 (HSV-1) were evaluated. Except for <b>1</b>, the other ten tested compounds exhibited cytotoxicity against HL-60 cells, with the IC₅₀ values of <b>3</b>, <b>4</b>, <b>6</b>, <b>7</b>, <b>11</b>, and <b>12</b> being closer to or rather lower than that of the positive control cisplatin. Additionally, all tested compounds demonstrated anti-HSV-1 activity, with seven compounds, i.e., <b>3</b>, <b>6</b>, <b>9</b>, <b>10</b>, <b>22</b>, <b>23</b>, and <b>24</b>, having EC₅₀ values lower than or comparable to that of the positive control acyclovir.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 4","pages":"845 - 862"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMR-based metabolomics for unraveling oleo-gum resin metabolome of rare Commiphora species: insights into taxonomic variation and tree sex differences","authors":"Tarik A. Mohamed,&nbsp;Ahmed Zayed,&nbsp;Emad A. AlSherif,&nbsp;Mohamed A. Farag,&nbsp;Hossam M. Abdallah","doi":"10.1007/s11418-025-01914-6","DOIUrl":"10.1007/s11418-025-01914-6","url":null,"abstract":"<div><p><i>Commiphora</i> species, valued for their resinous cell saps rich in terpenoids and other compounds, are known for their therapeutic benefits. This study aimed to be the first NMR-based metabolome profiling of oleo-gum resin derived from endemic rare <i>Commiphora</i> species. Insights into taxonomic variation and tree sex differences were targeted for future correlation with bioactivities-related assays. Oleo-gum resins and cell sap were collected and extracted by methanol from four naturally growing <i>Commiphora</i> species, including <i>C. gileadensis</i>, <i>C. quadricincta</i>, <i>C. kataf</i> female, and <i>C. kataf</i> male. Afterward, NMR acquisition and spectra interpretation were carried out, including various 1D and 2D-techniques. A total of 36 metabolites were identified, including 3 cycloartane derivatives, 12 amino acids and their derivatives, 7 organic acids, 1 phenolic acid, 6 sugars and sugar alcohols, 6 terpenoids, and 1 nitrogenous compound. Multivariate analysis, employing both unsupervised and supervised modeling, facilitated classification of samples and provided a foundation for future authentication and quality control of these taxa. Notably, <i>C. gileadensis</i> cell sap and <i>C. quadricincta</i> oleo-gum resin were metabolically distinct, enriched in terpenoids such as cycloartane 24-en-1,2,3-triol (<b>1</b>) and 1-acetoxycycloartan-24-ene-2,3-diol (<b>2</b>), while trehalose (<b>24</b>) was more abundant in other species. Further, quantitative NMR (qNMR) quantified 9 metabolite markers detected at high levels in <i>Commiphora</i> accessions. In conclusion, terpenoids were found to be abundant and discriminant compounds in <i>Commiphora</i> products. The results shall aid in the future standardization of <i>Commiphora</i> oleo-gum resins to be included in nutraceuticals and for future correlation with bioactivities-related assays.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 4","pages":"807 - 820"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186210","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":"Overwhelming glycyrrhizin production in Glycyrrhiza glabra induced by rihizobial symbiosis","authors":"Shion Yamamoto,&nbsp;Aya Shimomura,&nbsp;Satoshi Watanabe,&nbsp;Mareshige Kojoma,&nbsp;Akihiro Suzuki","doi":"10.1007/s11418-025-01918-2","DOIUrl":"10.1007/s11418-025-01918-2","url":null,"abstract":"<p>We reported that <i>Glycyrrhiza uralensis</i> inoculated with rhizobium tended to increase biomass production and glycyrrhizic acid (GL) production, in this study we have also achieved drastically increase in biomass and GL production in <i>Glycyrrhiza glabra</i>. At thirty days after inoculation (DAI), a significant increase in SPAD values was observed, and the expression of GL synthesis marker genes was also significantly increased. At 150 DAI, a significant increase in biomass was observed. Characteristically, it was also found that thick roots were enlarged by rhizobial inoculation. In addition, the expression of GL synthesis marker genes was also significantly increased. Moreover, GL content per unit root dry weight reached 4%, and GL production per plant increased six times compared to uninoculated plants. Moreover, we tried to reveal the mechanism of induction of GL production by rhizobial inoculation. Since it has been reported that the expression of jasmonic acid (JA) synthesis marker genes is increased by rhizobium in soybean, we investigated the expression of those genes in <i>G. glabra</i>, and found that <i>GgMYC2</i> and <i>GgJAR1</i> were up-regulated at Thirty DAI. Furthermore, methyl jasmonate treatment increased the expression of GL synthesis marker genes, suggesting that JA signaling is involved in the increased GL production due to rhizobial inoculation. These results aid in understanding the mechanism of increased GL production through the introduction of rhizobial symbiosis, and show the potential for providing a technology to significantly shorten the cultivation period for the production of <i>Glycyrrhiza</i> that meets the criteria for herbal medicines.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 4","pages":"833 - 844"},"PeriodicalIF":2.5,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A plasma metabolomic analysis revealed the metabolic regulatory mechanism of the water extract of Dendrobium huoshanense in improving streptozotocin-induced type 1 diabetes model rats","authors":"Hai-jun Xu,&nbsp;Zhen Zhang,&nbsp;Ya-fei Zhang,&nbsp;Shu-nan Cuan,&nbsp;Zhe Jia","doi":"10.1007/s11418-025-01909-3","DOIUrl":"10.1007/s11418-025-01909-3","url":null,"abstract":"<div><p><i>D. huoshanense</i> is a traditional Chinese medicine with antidiabetes effects, but the underlying metabolic regulatory mechanism remains unknown. Plasma metabolomic analysis was applied to assess the metabolic regulatory mechanism underlying the alleviation of streptozotocin-induced type 1 diabetes (STZ-T1D) by <i>D. huoshanense</i>. The successfully STZ-T1D model rats were assigned to the model group, the model + water extract of <i>D. huoshanense</i> (DHWE) group, and the model + metformin (MET) group. They were administered the corresponding medication by gavage. After 28 days, the plasma levels of glucose, malondialdehyde (MDA), C-reactive protein (CRP), and total antioxidant capacity (T-AOC) were determined. Morphological changes in the pancreatic islet tissue were analyzed via hematoxylin and eosin (H&amp;E) staining. The expression of occludin-1, zonula occludens protein 1 (ZO-1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) in the ileum tissue was determined via western blotting. Nontargeted metabolome analysis of the plasma was performed via ultrahigh-performance liquid chromatography. The results revealed that DHWE reduced blood glucose, C-reactive protein, and MDA levels; increased plasma T-AOC; improved intestinal mucous integrity and pancreatic islet morphological structure; and alleviated intestinal endoplasmic reticulum stress. Plasma metabolomics revealed that DHWE significantly increased the levels of ascorbic acid 2-sulfate, L-thyroxine, phosphatidylcholine (PC) (14:0e/5:0), and PC (16:1e/4:0); decreased the levels of D-(-)-fructose and indole-3-lactic acid; and significantly affected ascorbate and aldarate metabolism and glyoxylate and dicarboxylate metabolism in STZ-T1D rats (p &lt; 0.05), and the effects on the citric acid cycle and pyruvate metabolism tended to be significant (p &lt; 0.1). This study confirmed that DHWE alleviated STZ-T1D by reducing oxidative stress and the inflammatory response, enhancing intestinal mucosa integrity and affecting mainly the energy metabolism and vitamin C metabolism of STZ-T1D rats.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 4","pages":"750 - 772"},"PeriodicalIF":2.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109375","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":"Safranal ameliorates atherosclerosis progression partly via repressing PI3K/Akt and NF-κB signaling pathways in ApoE (−/−) mice","authors":"Yining Geng,&nbsp;Manping Song,&nbsp;Bing Huang,&nbsp;Ru Lin,&nbsp;Shiwen Wu,&nbsp;An Lin","doi":"10.1007/s11418-025-01913-7","DOIUrl":"10.1007/s11418-025-01913-7","url":null,"abstract":"<div><p>Atherosclerosis (AS) remains the main cause of vascular diseases. This study reveals the effects of safranal and underlying mechanisms in RAW264.7 macrophages under AS context, which is hoped to facilitate its clinical application. Safranal reduced AS progression in ApoE (−/−) mice, and it also increased the serum level of HDL-C and decreased the levels of TG, TC, and LDL-C as well as ALT and AST. Besides, safranal repressed the pathophysiological processes of OS (downregulated levels of ROS and MDA and upregulated biosynthesis of GSH), ERS (decreased protein levels of activating transcription factor 6, X-Box Binding Protein 1, and glucose-regulated protein, 78 kDa), and inflammation (downregulated serum levels of TNF-α, IL-1β, and IL-6) in vivo. Mechanistically, safranal repressed PI3K/Akt and NF-κB signaling pathways in vivo. On the cellular level, safranal treatment relieved the uptake of ox-LDL, and decreased contents of TG, TC, and LDL-C while increasing HDL-C level in ox-LDL-treated RAW264.7 macrophages. It also reduced the molecular indexes of pathophysiological processes (OS, ESR, and release of inflammatory mediators) in ox-LDL-exposed RAW264.7 macrophages. Notably, safranal treatment also impaired PI3K/Akt and NF-κB signaling pathways in ox-LDL-exposed RAW264.7 macrophages. Additionally, the PI3K agonist 740Y-P notably reversed the in vitro inhibitory effects of safranal on lipid deposition, productions of TC and TNF-α, and protein levels of molecules of PI3K/Akt and NF-κB signaling pathways. Safranal exerts anti-AS effects via repressing OS, ERS, and inflammation in ApoE (−/−) mice, and it also negatively modulates PI3K/Akt and NF-κB signaling pathways in RAW264.7 macrophages. </p><h3>Graphical abstract</h3><p>Safranal reduces oxidative stress, endoplasmic reticulum stress, and release of inflammatory factors to relieve atherosclerosis progress partly via repressing PI3K/Akt and NF-κb pathways in RAW264.7 macrophages.</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 4","pages":"821 - 832"},"PeriodicalIF":2.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957551","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}