Journal of Natural Medicines最新文献

{"title":"Diosmetin alleviates osteoarthritis through modulating the polarization of macrophages by inhibiting the PI3K/Akt signaling pathway.","authors":"Shaoju Ren, Wang Zeng, Zhangyu Du, Juan Dai, Xueyi Li, Hao Wang, Yuqin Liu, Ruidong Li, Jianhui Liu","doi":"10.1007/s11418-025-01916-4","DOIUrl":"https://doi.org/10.1007/s11418-025-01916-4","url":null,"abstract":"<p><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>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"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, Michiho Ito","doi":"10.1007/s11418-025-01934-2","DOIUrl":"https://doi.org/10.1007/s11418-025-01934-2","url":null,"abstract":"<p><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>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"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, Jia Yue, Shaolei Luo, Hongkun Bao, Jie Bai","doi":"10.1007/s11418-025-01933-3","DOIUrl":"https://doi.org/10.1007/s11418-025-01933-3","url":null,"abstract":"<p><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 Ganoderic acid A (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>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"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}

{"title":"Apoptosis-inducing activity of a steroidal glycoside from Allium chinense G. Don. bulbs in human small-cell lung cancer cells via mitochondrial dysfunction and ER stress.","authors":"Tamami Shimazaki, Tomoki Iguchi, Aki Kanda, Ami Shirakawa, Yoshihiro Mimaki","doi":"10.1007/s11418-025-01932-4","DOIUrl":"https://doi.org/10.1007/s11418-025-01932-4","url":null,"abstract":"<p><p>A saponin fraction from Allium chinense G. Don. bulbs has previously been reported to exhibit cytotoxicity against melanoma and carcinoma cell lines; however, the active compounds responsible for this cytotoxicity have not been identified. A phytochemical investigation was conducted on A. chinense bulbs to identify novel anticancer seeds from natural products. Seven steroidal glycosides (1-7), comprising three spirostan-type (1-3) and four furostan-type (4-7), were obtained. This is the first report of the isolation of 6 and 7 from A. chinese. The cytotoxicity of 1-7 was evaluated in SBC-3 human small-cell lung cancer cells using the MTT assay. Compounds 2, 3, and 5 demonstrated moderate cytotoxicity against SBC-3 cells, with IC₅₀ values ranging from 15 to 42 μM dose-dependently. Compound 3, (25R)-3β-[(O-α-L-arabinopyranosyl-(1 → 6)-O-[β-D-xylopyranosyl-(1 → 4)]-β-D-glucopyranosyl)oxy]-5α-spirostan-6-one, which exhibited the most potent cytotoxicity among the isolated compounds, induced caspase-dependent apoptotic cell death via both mitochondrial dysfunction leading to reactive oxygen species (ROS) release and endoplasmic reticulum stress caused by ROS. Furthermore, since calreticulin exposure on the outer leaflet of the plasma membrane and extracellular ATP release were observed in SBC-3 cells treated with 3, it may elicit immunogenic cell death in SBC-3 cells.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615754","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":"Ameliorative role of Polyscias fruticosa leaf extract in aluminum chloride-induced neurotoxicity flies possibly mediated by N-methyl-D-aspartate receptor antagonistic and anticholinesterase active compounds.","authors":"Dao Thi Anh Phan, Hien Phung Le, Tran Huyen Tran, Ut Van Le, Minh Van Le, Trieu Hai Ly","doi":"10.1007/s11418-025-01928-0","DOIUrl":"https://doi.org/10.1007/s11418-025-01928-0","url":null,"abstract":"<p><p>Polyscias fruticosa leaves have been used in traditional medicine to aid in the therapy of brain and nerve-related disorders, including dementia. However, the evidences for the effects and mechanisms of P. fruticosa leaf extract (PFLE) and its constituents in improving dementia remain unclear. This study aims to evaluate the ameliorative effect of PFLE in aluminum chloride-induced neurotoxicity Drosophila melanogaster model. Simultaneously, the dementia-improving mechanisms of PFLE's compounds were explored by computational pharmacological analysis. Results showed that D. melanogaster exposed to 1.0, 2.0, and 4.0 mg/mL PFLE or 0.1 mg/mL donepezil hydrochloride had significant improvements in lifespan, memory, motor behavior, and oxidative stress markers, including decreased malondialdehyde level and increased glutathione level in flies' homogenates. Also, PFLE had acetylcholinesterase inhibitory ability with an IC₅₀ value of 266.10 µg/mL. Applying the UHPLC-Q-TOF-MS/MS technique, 36 compounds were identified in the PFLE. Among these, 25 compounds, including acid amines, flavonoids, saponins, choline, piperine, and vitamin B1, have been demonstrated potential for supporting the treatment of Alzheimer's disease (AD). Interestingly, molecular docking study indicated that many of the compounds are agents of prominent targets in dementia treatment including N-methyl-D-aspartate (NMDA) receptor and cholinesterase, in which polyscioside A-E are the main components of the PFLE that may be responsible for the NMDA receptor antagonistic and anticholinesterase activities. These compounds have favorable physiochemical properties and drug-likeliness. This study suggested the potential of the PFLE and its compounds in the prophylactic and treatment of neurodegenerative pathologies, including AD, and laid the foundation for further studies.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615710","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":"Drimane sesquiterpenoids from cultures of basidiomycete Ganoderma subresinosum.","authors":"Arunrat Yangchum, Malipan Sappan, Wilunda Choowong, Tuksaporn Thummarukcharoen, Thitiya Boonpratuang, Masahiko Isaka, Prapairat Seephonkai","doi":"10.1007/s11418-025-01931-5","DOIUrl":"https://doi.org/10.1007/s11418-025-01931-5","url":null,"abstract":"<p><p>Nine previously undescribed drimane sesquiterpenoids, ganoresinosins A-I (1-9), were isolated from cultures of basidiomycete Ganoderma subresinosum. The absolute configuration of ganoresinosin H (8) was determined using the modified Mosher's method. Ganoresinosin A (1) showed antimalarial activity against Plasmodium falciparum K1 (IC₅₀ 34 μM), whereas ganoresinosin E (5) exhibited antitubercular activity against Mycobacterium tuberculosis H37Ra (MIC 12.5 μg/mL).</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574640","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":"Metabolite derived from green tea polyphenol increases and activates plasmacytoid dendritic cells.","authors":"Motofumi Kumazoe, Misato Nakajima, Reno Kawamoto, Yoshinori Fujimura, Reno Tomioka, Moeto Suzuki, Yuko Tanaka, Hirofumi Tachibana","doi":"10.1007/s11418-025-01929-z","DOIUrl":"https://doi.org/10.1007/s11418-025-01929-z","url":null,"abstract":"<p><p>The immune system plays a crucial role in protecting the body from harmful bacterial, viral infections and vital for cancer suppression. Dendritic cells (DCs) are indispensable mediators that facilitate the connection between innate and acquired immunity via antigen presentation and cytokine production. One of the major intestinal microbial metabolites of green tea polyphenols, 5-(3',5'-dihydroxyphenyl)-γ-valerolactone (EGC-M5), enhances T cell activity. However, the detailed underlying mechanisms remain unknown. Here, we revealed that the oral administration of EGC-M5 increases and activates plasma cytoid dendritic cells (pDCs) in the spleen without causing changes in body weight. Consistent with these findings, administration of EGC-M5 increased the gene expression of interleukin-12 in the spleen. Oral administration of EGC-M5 significantly increased type I Interferon (IFN) and IL-6 levels, which are involved in vaccine-induced antibody production. Ex vivo experiments showed that EGC-M5 treatment did not directly enhance pDC differentiation. In conclusion, EGC-M5 indirectly increased pDC levels in vivo, accompanied by an increase in the expression of pDC activation markers and the gene expression of interleukin-12, type I IFN and IL-6 in the spleen.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566952","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":"Multi-omics analysis reveals the mechanism of action of Atractylodin against depression.","authors":"Shengchuan Bao, Mei Feng, XiZhen Zhang, Mingjun Xie, Jing Teng","doi":"10.1007/s11418-025-01930-6","DOIUrl":"https://doi.org/10.1007/s11418-025-01930-6","url":null,"abstract":"<p><p>Atractylodin (ATR) is a natural sesquiterpene compound primarily isolated from the rhizomes of Atractylodes, a plant of the Asteraceae family. It is the core bioactive component of the traditional Chinese medicine Atractylodes and has been confirmed to possess anti-inflammatory, antioxidant, and neuroregulatory functions in various disease models. Recent studies have highlighted ATR's significant roles in anti-tumor, anti-inflammatory, and immune-regulatory activities. However, it remains unclear whether ATR can alleviate depression and its potential pharmacological mechanisms. Our study demonstrates that ATR treatment alleviated depression-like behaviors and improved neuronal changes in the hippocampus of rats. Transcriptomic and proteomic analyses revealed that ATR exerted its antidepressant effects primarily through the regulation of ferroptosis and synaptic plasticity. ATR increased the expression of IL-10, SOD, and GSH, while reducing IL-1β, TNF-α, MDA, and ROS levels, thereby improving inflammation and oxidative stress. Immunohistochemical results indicated that ATR treatment significantly increased the expression of GPX4, SLC7A11, BDNF and NRF2 proteins. This study demonstrates that ATR significantly alleviates depressive symptoms in CUMS rats, with its mechanism primarily involving the regulation of ferroptosis and improvement of synaptic plasticity. ATR may be a potential candidate as an antidepressant.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558761","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-cancer activity of the glycyrrhetinic acid derivatives with an inhibitory inflammatory microenvironment.","authors":"Jianrong Liu, Tianbo Wu, Wei Li, Quanyi Zhao, Dian He","doi":"10.1007/s11418-025-01926-2","DOIUrl":"https://doi.org/10.1007/s11418-025-01926-2","url":null,"abstract":"<p><p>The tumor inflammatory microenvironment plays an important role in tumor development, and the compounds which modulate tumor microenvironment can be able to accelerate tumor cell death. Here, compound 1 was screened and evaluated through both inhibiting cancer cell proliferation and alleviating the inflammation in microenvironment. In the anti-cancer cell proliferation assay, compound 1 displayed strong proliferative inhibition against all six cell lines, with IC₅₀ values in the range 2-6 μM; among them, the HCT116 cell line was the most sensitive to compound 1. Second, compound 1 showed better inflammatory activities in RAW264.7 cell model than the control GA and 5-FU; it not only decreased the NO level in a concentration-dependent manner, but also reduced the TLR4, HMGB1, IL-1β, TNF-α, iNOS and COX-2 levels; moreover, compound 1 also strongly inhibited NO produce in A549, HEPG2, and HCT116 cells, and it displayed the best for HCT116 cells, with an IC₅₀ value of 2.04 ± 0.68 μM. Third, compound 1 decreased the MMP and increased ROS levels in HCT116 cells; and it upregulated the expression levels of Bax and Cyt-C, and downregulated the Bcl-2 level, finally activating caspase-3 to promote the HCT116 cells apoptosis. This indicates compound 1 had an anti-HCT116 activity possibly by inhibiting the inflammatory factors in microenvironment, as well as by inducing HCT116 cells apoptosis. In animal tests, compound 1 reduced the volume and weight of tumor, indicating it has an obvious anti-tumor effect. Overall, compound 1 is a multi-target drug for the treatment of colon cancer, and it has the potential to be an anti-colon cancer drug candidate.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551621","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":"Natural products that target p53 for cancer therapy.","authors":"Sachiko Tsukamoto","doi":"10.1007/s11418-025-01906-6","DOIUrl":"10.1007/s11418-025-01906-6","url":null,"abstract":"<p><p>Wild-type p53 acts as a tumor suppressor, but p53 is frequently mutated and inactivated in tumor cells, promoting cancer progression, invasion, and metastasis. Thus, compounds that reactivate p53 may be leveraged for cancer treatment, and the development of drugs targeting p53 reactivation is actively progressing. Notably, natural products exhibit diverse structures and biological activities and are used as therapeutic agents for various diseases worldwide. This review discusses the natural products that inhibit p53 degradation through p53-Mdm2 interaction, promote p53 reactivation by inducing conformational changes, and exhibit p53-dependent growth inhibition.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":"725-737"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957796","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}