Journal of Natural Medicines最新文献

{"title":"Discovery of active compounds in Danshen–Chuanxiong formula for blood–brain barrier protection: a multi-parametric study using an OGD/R-induced spheroid model","authors":"Yue Zhou,&nbsp;Yiran Li,&nbsp;Zhenzhong Yang,&nbsp;Lu Zhao,&nbsp;Yule Wang","doi":"10.1007/s11418-025-01939-x","DOIUrl":"10.1007/s11418-025-01939-x","url":null,"abstract":"<div><p>Blood–brain barrier (BBB) dysfunction is a well-established pathological phenotype of ischemic stroke, and targeting BBB integrity has emerged as a promising therapeutic strategy. Danshen-Chuanxiong formula (DS-CX), an effective herbal combination against ischemic stroke, has demonstrated regulatory effects on the BBB at various stages of ischemic stroke. However, its specific BBB-protective components and underlying molecular mechanisms remain unclear. Recent advances in multicellular self-assembled BBB spheroids have shown distinct advantages in disease modeling and drug discovery, offering a novel approach to address these questions. To simulate ischemic stroke-induced BBB dysfunction, we developed an oxygen–glucose deprivation/reoxygenation (OGD/R)-induced BBB disruption model using multicellular spheroids. To identify the effective substances of DS-CX responsible for BBB protection, we conducted a multi-parametric evaluation to assess BBB permeability, tight junctions, cell viability, reactive oxygen species (ROS) levels, inflammatory markers, and apoptotic phenotypes using high-content imaging. Further immunofluorescence and transcription analyses were performed to elucidate the BBB-protective mechanisms of DS-CX and its active components. Similar to the overall effects of DS-CX on BBB protection, preliminary screening fortunately found that both protocatechuic acid, ferulic acid, and senkyunolide I significantly reduced OGD/R-induced leakage, and upregulated the protein and mRNA levels of ZO-1 and Claudin-5 in BBB spheroids. Further multi-phenotypic assessments manifested that DS-CX and its active compounds effectively improved cell survival, reduced ROS production, inhibited inflammation, and decreased apoptosis, compared to the damaged BBB spheroids without drug intervention. Molecular experiments showed that DS-CX and its active constituents not only rescued the abnormal protein levels of pivotal targets related to oxidative stress (HO-1), inflammation (MMP-9, TLR-4), and apoptosis (Caspase-3, Bax, Bcl-2) in OGD/R-treated BBB spheroids, but also normalized the dysregulated mRNA levels of vWF, HO-1, MMP-9, TLR-4, TNF-α, IL-6, IL-1β, and IL-18 caused by OGD/R stimulation. Collectively, the present work successfully identified protocatechuic acid, ferulic acid, and senkyunolide I as key BBB-protective components of DS-CX against ischemic stroke. These compounds likely exert their therapeutic effects through multi-target regulation of oxidative stress, inflammation, and apoptosis. Our findings provide a novel spheroid-based multi-parametric screening approach for discovering BBB-targeted therapies in ischemic stroke.</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":"1122 - 1139"},"PeriodicalIF":2.5,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803222","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":"Berberine attenuates the expression of NLRP3 and downstream inflammasome effectors in diabetic retinopathy","authors":"Na Li,&nbsp;Ji-Lin Chen,&nbsp;Yi-Jian Sun,&nbsp;Jia-Fan Sun,&nbsp;Ting-Hua Wang,&nbsp;Amy Yi Hsan Saik,&nbsp;Alan Han-Kiat Ong","doi":"10.1007/s11418-025-01935-1","DOIUrl":"10.1007/s11418-025-01935-1","url":null,"abstract":"<div><p>The objective of this study is to investigate the protective effects of berberine (BBR) on diabetic retinopathy (DR) and its regulatory mechanism on NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway. DR rat model was established by Streptozotocin (STZ) injection and treated with BBR. Retinal structure was evaluated by Optical Coherence Tomography (OCT), Hematoxylin and Eosin (HE) staining, and immunofluorescence. NLRP3 pathway proteins were detected by Western blot (WB), and the effects were further studied using RNA interference. BBR significantly improved retinal structure in DR rats and decreased the expression of NLRP3, Cysteine-aspartic acid protease-1(Caspase-1), Gasdermin D (GSDMD), Interleukin-1 beta (IL-1β), and Interleukin-18 (IL-18) (<i>p</i> &lt; 0.05). In an in vitro study using human RPE cells line, BBR administration improved cell viability and reduced RPE pyroptosis, while RNA interference of NLRP3 pathway enhanced BBR’s protective effects. BBR ameliorates DR by inhibiting NLRP3 inflammasome-mediated pyroptosis pathway.</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":"1091 - 1105"},"PeriodicalIF":2.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-neuroinflammatory effects of epivernodalol, a sesquiterpene from Vernonia anthelmintica (L.) Willd., in lipopolysaccharide-stimulated murine microglial cells","authors":"Shengnan Ma,&nbsp;Yue Wang,&nbsp;Sheng-An Tang","doi":"10.1007/s11418-025-01937-z","DOIUrl":"10.1007/s11418-025-01937-z","url":null,"abstract":"<div><p>Four terpenes—epivernodalol [Epl], cynaropicrin, vernonilide A, and vernodalin—were isolated from <i>Vernonia anthelmintica</i> (L.) Willd., and their effects on interleukin (IL)-6 secretion in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells were evaluated. To elucidate the underlying mechanisms of their immunomodulatory activity, we quantified the mRNA levels of key cytokines (IL-1β, TNF-α, IL-6, IL-10, and TGF-β) and the expression of CD206 using qRT-PCR. Additionally, surface markers of BV2 cells were analyzed via flow cytometry. Furthermore, we assessed the phosphorylation of NF-κB and its inhibitory protein, IκB, in BV2 microglial cells by western blotting. Our findings demonstrated that Epl exerts anti-neuroinflammatory effects by suppressing NF-κB pathway activation and pro-inflammatory cytokine secretion while enhancing anti-inflammatory cytokines production and promoting M2 polarizations. This study not only reveals a previously unrecognized role of Epl but also provides insights into the identification of novel therapeutic targets for neuroinflammatory diseases.</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":"1226 - 1235"},"PeriodicalIF":2.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797896","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":"Investigation and development of natural products that target chemotherapy resistance factors in cancer cells","authors":"Takahiro Matsumoto","doi":"10.1007/s11418-025-01942-2","DOIUrl":"10.1007/s11418-025-01942-2","url":null,"abstract":"<div><p>Heat shock proteins (HSPs) play an important role in several tumors; contribute to anti-cancer drug resistance, cell proliferation, and metastasis; and have been suggested as a major cause of failed anti-cancer drug treatment. In addition, cancer stem cells (CSCs) have been identified in many types of malignancies, including leukemia, breast, colorectal, and brain cancers, and are a leading cause of failed cancer treatment owing to their anti-cancer drug and radiation therapy resistance. Therefore, many researchers, including our group, have investigated and developed natural products that target chemotherapy resistance factors in cancer cells. This review introduces the inhibitors of chemotherapy resistance factors discovered using a unique assay system.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"1005 - 1016"},"PeriodicalIF":2.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-025-01942-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797898","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":"Metabolism of coclaurine into the WADA-banned substance higenamine: a doping-relevant analytical evaluation of Kampo extracts","authors":"Seiichi Sakamoto,&nbsp;Kouta Osaki,&nbsp;Hiroko Abe,&nbsp;Yorie Tayama,&nbsp;Akito Tsuruta,&nbsp;Poomraphie Nuntawong,&nbsp;Satoru Koyanagi,&nbsp;Varalee Yodsurang,&nbsp;Satoshi Morimoto","doi":"10.1007/s11418-025-01940-4","DOIUrl":"10.1007/s11418-025-01940-4","url":null,"abstract":"<div><p>Higenamine, a β2-agonist, has been listed as a prohibited substance by the World Anti-Doping Agency (WADA) since 2017, poses a doping risk through the use of traditional herbal formulations. In Japan, Kampo medicines, composed of multiple crude drugs, are widely used, raising concerns about the unintentional intake of banned substances. In this study, urinary excretion of higenamine was observed in mice following coclaurine administration, and higenamine formation was confirmed in human liver microsomes, indicating a potential risk associated with coclaurine-containing herbs. Therefore, 128 Kampo extract products were analyzed to identify crude drugs containing higenamine and/or coclaurine using lateral flow immunoassay (LFA), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. Consequently, fourteen crude drugs were identified to contain higenamine and/or coclaurine. Notably, six crude drugs—including Magnolia bark, Japanese Zanthoxylum peel, Jujube seed, Magnolia flower, Cimicifuga rhizome, and Coptis rhizome—were newly confirmed to contain higenamine, while nine—including Cinnamon bark, Magnolia bark, Euodia fruit, Asiasarum root, Japanese Zanthoxylum peel, Cimicifuga rhizome, Jujube, Processed Aconite root, and Phellodendron bark—were newly identified as containing coclaurine. These results underscore the potential risk of doping violations associated with coclaurine, which may be metabolized into higenamine, although coclaurine is not currently classified as a prohibited substance. Our findings highlight the need for regulatory consideration to mitigate unintentional doping risks among athletes using Kampo medicine.</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":"1140 - 1153"},"PeriodicalIF":2.5,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768267","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":"Unprecedented triterpenes with anti-inflammatory activity from Limax maximus","authors":"Ya-feng Wang,&nbsp;Pei-de Tang,&nbsp;Rui-jie He,&nbsp;Zhang-bin Liu,&nbsp;Yong-qiong Wei,&nbsp;Jun Ruan,&nbsp;Bing-yuan Yang,&nbsp;Yong-lin Huang","doi":"10.1007/s11418-025-01936-0","DOIUrl":"10.1007/s11418-025-01936-0","url":null,"abstract":"<div><p>Four triterpenes with the unprecedented pentacyclic skeletons were isolated from <i>Limax maximus</i>, the traditional medicine of the Zhuang ethnic group in Guangxi. Notably, compounds <b>1</b>−<b>4</b> were characterized by rare 7/6/5 tricyclic ring moiety linked to 6/5 bicyclic moiety via three carbon chain. The structures of compounds <b>1</b>−<b>4</b> were elucidated by comprehensive spectroscopic analysis. The absolute configurations of compounds <b>1</b>−<b>2</b> were determined by single-crystal X-ray diffraction analysis using Cu Kα radiation. Biogenetically, compound <b>1</b> could be derived from the tetraepoxysqualenes, via cyclisation and hydroxylation reactions. Bioactivity assay results showed that compound <b>4</b> significantly inhibited LPS-induced NO production in RAW 264.7 cells at 25 µM with inhibition of NO production by 47%.</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":"1216 - 1225"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-allergic actions and pharmacokinetics of orally administered 18α-glycyrrhetinic acid and 18β-glycyrrhetinic acid in mice","authors":"Mitsuhiko Nose,&nbsp;Cheri Fukaya,&nbsp;Shinsuke Hisaka","doi":"10.1007/s11418-025-01941-3","DOIUrl":"10.1007/s11418-025-01941-3","url":null,"abstract":"<div><p>In this study, we explored the anti-allergic actions of 18α-glycyrrhetinic acid and 18β-glycyrrhetinic acids (18α-GA and 18β-GA), to compare the pharmacological properties of these stereoisomers and to clarify the immunopharmacological contribution of 18α-glycyrrhizin in licorice. 18β-GA exhibited anti-allergic effects in murine models of contact dermatitis and IgE-mediated immediate allergic dermatitis, whereas 18α-GA showed no such effects. To elucidate the mechanism underlying this variation, the blood concentrations of 18α-GA and 18β-GA were measured after the oral administration of both compounds; we detected only 18β-GA in sera. We also demonstrated that considerable amounts of 18α-GA remained in the small intestine, which indicates low absorption of 18α-GA from the gastrointestinal tract. In addition, 18α-GA, like 18β-GA, directly suppressed IgE-mediated degranulation in RBL-2H3, and both showed equivalent clearance after intravenous administration. In conclusion, 18α-GA was not absorbed through the gastrointestinal tract in mice and did not exhibit the anti-allergic actions exhibited by 18β-GA. To clarify the differences in absorbability between these two compounds further research focusing on the gastrointestinal absorption of 18β-GA is needed.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"1236 - 1242"},"PeriodicalIF":2.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740798","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":"Diosmetin alleviates osteoarthritis through modulating the polarization of macrophages by inhibiting the PI3K/Akt signaling pathway","authors":"Shaoju Ren,&nbsp;Wang Zeng,&nbsp;Zhangyu Du,&nbsp;Juan Dai,&nbsp;Xueyi Li,&nbsp;Hao Wang,&nbsp;Yuqin Liu,&nbsp;Ruidong Li,&nbsp;Jianhui Liu","doi":"10.1007/s11418-025-01916-4","DOIUrl":"10.1007/s11418-025-01916-4","url":null,"abstract":"<div><p>Osteoarthritis (OA) is the most common degenerative musculoskeletal disorder worldwide. Diosmetin is the aglycone of diosmin, which is widely distributed in citrus fruits and olive leaves and expresses anti-inflammatory effects in many diseases. It was reported to alleviate OA through inhibiting subchondral bone remodeling, but its anti-inflammatory function in attenuating OA has not been determined. In this study, we established an OA mouse model by anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgery. Diosmetin was then intragastrically administered twice a week for eight weeks. The effect of diosmetin on the mouse knee joint was determined via histopathological analysis. In vitro, diosmetin was applied to treat chondrocytes, fibroblast-like synoviocytes (FLSs), and macrophages. The effect of macrophage secretion on chondrocytes was evaluated using a coculture system. The activation of the PI3K/Akt pathway in macrophages was evaluated via Western blotting. The results showed that diosmetin attenuated OA in an OA mouse model without causing obvious organ toxicity. Diosmetin did not inhibit the degradation of the extracellular matrix or the upregulation of degrading enzymes in chondrocytes. Diosmetin also did not inhibit the expression of fibrosis-related proteins in FLSs. Diosmetin promoted the transition of macrophages from the M1 to the M2 phenotype through inhibiting the PI3K/Akt pathway. The coculture of chondrocytes and macrophages indicated that cytokines secreted by macrophages attenuated the degradation of the cartilage extracellular matrix. To conclude, diosmetin promoted the transition of macrophages from the M1 to the M2 phenotype. Diosmetin-treated macrophages attenuated the degradation of the cartilage extracellular matrix, which may be another mechanism underlying the protective effect of diosmetin on OA.</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":"1030 - 1043"},"PeriodicalIF":2.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697339","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":"Advanced multidimensional quality evaluation of encapsulated peppermint oil products in various formulas","authors":"Mami Sogame,&nbsp;Michiho Ito","doi":"10.1007/s11418-025-01934-2","DOIUrl":"10.1007/s11418-025-01934-2","url":null,"abstract":"<div><p>We investigated the actual label indications and quality of encapsulated peppermint oil (PO) products marketed as medicinal products for irritable bowel syndrome (IBS) or health food. Quality was multidimensionally evaluated with regard to the original plant source, content of PO and components of safety concern, and formulation. The original plant source was evaluated with reference to the criteria specified in the British and European pharmacopoeias and advanced GC–MS profiling tests, combined with simple discriminant analysis of the major 4 components (menthol, menthone, menthofuran, and isomenthone), which enabled evaluation of the various PO product formulations. 10 samples of 8 medicinal products and 40 samples of health food products were tested. Results showed that 2 medicinal products and 18 health food products were suspected of using material similar to mentha oil, which is frequently confused with PO. Menthol quantitative analysis showed that one medicinal product and 6 health food products contained different amounts of PO content from the indicated amounts. Further, one medicinal product and one health food product contained high levels of components of safety concern. Formulation quality was evaluated by the disintegration test, which found that 3 medicinal products and 15 health food products were not compliant. These results suggest that the quality of some PO products is inadequate. In particular, all health food products labeled with health claims related to IBS had problems in their quality or evidence of health claims.</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":"1243 - 1261"},"PeriodicalIF":2.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666810","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":"Ganoderic acid A ameliorated LPS-induced depression-like behaviors via suppression of acute neuroinflammation","authors":"Haoran Li,&nbsp;Jia Yue,&nbsp;Shaolei Luo,&nbsp;Hongkun Bao,&nbsp;Jie Bai","doi":"10.1007/s11418-025-01933-3","DOIUrl":"10.1007/s11418-025-01933-3","url":null,"abstract":"<div><p>Research context reveals that major depressive disorder (MDD), as a prevalent chronic relapsing psychiatric condition affecting up to one-third of patients with treatment resistance, necessitates urgent development of novel therapeutic agents. Emerging evidence implicates neuroinflammatory mechanisms in MDD pathophysiology, while the antidepressant potential of <i>Ganoderic acid A</i> (GAA), a triterpenoid compound derived from Ganoderma lucidum, particularly through modulation of lipopolysaccharide (LPS)-induced depression-like behaviors via acute neuroinflammation suppression remains underexplored. This study demonstrates for the first time that GAA administration significantly inhibits cerebral inflammatory activity and exhibits antidepressant properties in LPS-challenged murine models. Experimental protocols involved male C57BL/6 mice receiving intraperitoneal LPS injections (2 mg/kg) to establish depression-like phenotypes, with control and treatment groups administered saline or GAA (2.5 mg/kg) respectively. Behavioral assessments incorporating sucrose preference tests, forced swimming assays, and tail suspension evaluations were conducted. Neurobiological analyses quantified prefrontal cortex (PFC) protein expression of Iba1, iNOS, and GFAP through immunofluorescence techniques, with parallel measurements of caspase-1 and IL-1β levels using comparable methodology. Inflammatory cell infiltration in PFC regions was histologically evaluated via hematoxylin–eosin staining protocols.Key findings demonstrate that GAA intervention not only ameliorated LPS-induced depression-like behavioral manifestations but crucically modulated neuroinflammatory pathways through downregulation of microglial and astrocytic activation states in the PFC. Specific reductions in caspase-1 and IL-1β inflammatory mediators were quantitatively confirmed, substantiating the compound’s mechanism of action through targeted neuroimmune regulation. These results provide experimental validation for GAA’s therapeutic potential as an antidepressant agent operating via neuroinflammation suppression paradigms, offering critical insights for developing novel MDD treatments targeting inflammatory pathomechanisms.</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":"1188 - 1199"},"PeriodicalIF":2.5,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625239","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}