Journal of Natural Medicines最新文献

{"title":"Mechanism study of the effects of astragaloside IV and quercetin on idiopathic pulmonary fibrosis.","authors":"Ye Luo, Chang-Jun Xu, Xing-Hui Ai, Yu-Ping Li, Xing Zhu, Chang-Fu Yang","doi":"10.1007/s11418-025-01896-5","DOIUrl":"https://doi.org/10.1007/s11418-025-01896-5","url":null,"abstract":"<p><p>This study aimed to investigate the effects of astragaloside IV(AS-IV) and quercetin (QCT) on autophagic activity, pyroptosis, and epithelial-mesenchymal transdifferentiation (EMT) in the context of idiopathic pulmonary fibrosis (IPF), utilizing both in vivo and in vitro models. In the in vivo component of the research, C57BL/6 J mice were subjected to bleomycin (BLM) modeling, followed by AS-IV + QCT intervention at low, medium, and high doses for 14 and 28 days. Pathological changes in lung tissue were assessed through HE and Masson staining. Additionally, the expression levels of autophagy and pyroptosis-related proteins in serum and bronchoalveolar lavage fluid were examined via Western blot analysis. In the in vitro experiment, RAW264.7 macrophage cells were co-cultured with MLE-12 alveolar epithelial cells (3:1 ratio), implementing BLM and NLR family pyrin domain-containing protein (NLRP3) + BLM models to induce IPF. The effects of AS-IV and QCT on these cells were evaluated by electron microscopy to observe structural changes, while Western blot and ELISA were used to measure the expression of autophagy and pyroptosis-related proteins. Results showed that AS-IV and QCT significantly enhanced autophagic activity, evidenced by increased levels of LC3II and beclin-1 and decreased levels of P62. Additionally, both compounds reduced the expression of pyroptosis-related proteins (NLRP3, Caspase-1, IL-1β, and IL-18) and slowed the progression of EMT in alveolar epithelial cells. These findings propose that AS-IV and QCT inhibit the EMT process in IPF by activating autophagic mechanisms while suppressing pyroptosis, thereby underscoring their potential as innovative therapeutic strategies for IPF and highlighting the promising implications of herbal compounds in its prevention and treatment.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957606","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":"https://doi.org/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":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring anti-hyperglycemic potential of Pseuderanthemum crenulatum: isolation, structural elucidation and α-glucosidase inhibition evaluation.","authors":"Dung V Ngo, Le-Thu T Nguyen, Ngoc T N Ngo, Lien-Hoa D Nguyen, Binh T D Trinh","doi":"10.1007/s11418-025-01907-5","DOIUrl":"https://doi.org/10.1007/s11418-025-01907-5","url":null,"abstract":"<p><p>Pseuderanthemum crenulatum (Acanthaceae) is a medicinal plant traditionally used to manage diabetes. However, its chemical constituents remain unexplored as no studies have been conducted on this species to date. This study aimed to chemically characterize and evaluate the anti-hyperglycemic activity of compounds isolated from the stems and roots of P. crenulatum. The isolation process involved utilizing column chromatography techniques, while structures were characterized mainly by 1D and 2D NMR experiments. Anti-hyperglycemic activity was evaluated by measuring their inhibitory effects on the α-glucosidase enzyme. Following this, a new abietane-type dinorditerpenoid, namely pseuderanthemone (1), along with ten known compounds (2-11), was isolated from an ethyl acetate extract of the stems and roots of P. crenulatum. The investigation into their anti-hyperglycemic effects revealed that compounds 1-3, and 6-10 showed higher α-glucosidase inhibitory activity than positive control, acarbose. Among them, compound 9 demonstrated the most potent activity, with an IC₅₀ value nearly ten times lower than acarbose. Furthermore, kinetic analysis showed that compound 2 displayed mixed-type inhibition, and compound 3 demonstrated uncompetitive inhibition while the remaining compounds exhibited competitive inhibition.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957795","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":"Dendrobium huoshanense polysaccharide inhibits NSCLC proliferation and immune evasion via FXR1-IL-35 axis signaling pathway.","authors":"Xinying Zhu, Guoquan Yin, Jiaqian Xu, Xiaolei Tang, Fangliu Yu","doi":"10.1007/s11418-025-01894-7","DOIUrl":"https://doi.org/10.1007/s11418-025-01894-7","url":null,"abstract":"<p><p>Dendrobium huoshanense has received special attention for its advantages in the treatment of lung cancer, but the underlying molecular mechanisms are not yet well understood. First, we obtained 8 active ingredients and 159 effective action targets of Dendrobium huoshanense using network pharmacology, and searching target interactions through STRING, constructing the PPI network and KEGG, GO and Hallmark enrichment analysis. Then, we combined target's enrichment analysis and GSEA enrichment analysis of IL-35, indicating the mechanism of cDHPs for non-small cell lung cancer (NSCLC) may be related to tight junction and NSCLC pathway. Further, FXR1 and ACTR3 were identified as core therapeutic targets, and high expression of FXR1 or ACTR3 was significantly associated with poor prognosis of patients. The analysis of single-cell data also indicated that the percentage of CD4-CTLA4-Treg cells may be increased by the expression of IL-35, resulting in a suppressive immune microenvironment. Next, In vivo experiment, we detected iTr35 by flow cytometry, detected IL-35 level by RT-PCR, Western blotting and ELISA, and detected NK cell activity to explore the immunomodulatory effects and anti-tumor mechanism of cDHPs. After cDHPs administration, the conversion of CD4⁺ T cells to iTr35 is inhibited, p35 and EBI3 in both protein and mRNA levels, the levels of IL-35 and IL-4 in serum decreased. The levels of IFN-γ, while the activity of NK cells in mice increased, enhancing the anti-tumor immune effect of the organism. Finally, analysis of sequencing data from the immunotherapy cohort of tumor-bearing mice obtained from the TISMO database shows that the combination of cDHPs and PD-1/PD-L1 antibodies improves effector and thus PD-1/PD-L1 antibody efficacy. These findings suggest that cDHPs inhibit NSCLC proliferation and immune escape via the FXR1-IL-35 axis signaling pathway.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967686","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":"Potential of siphonaxanthin, a green algal carotenoid, to prevent obesity and related diseases.","authors":"Yuki Manabe, Tatsuya Sugawara","doi":"10.1007/s11418-025-01897-4","DOIUrl":"https://doi.org/10.1007/s11418-025-01897-4","url":null,"abstract":"<p><p>The increasing prevalence of obesity and its related diseases, including diabetes mellitus and metabolic dysfunction-associated fatty liver disease, has become a significant social problem. These diseases are believed to be preventable through healthy diet and exercise habits, and the investigation of food ingredients that are useful for prevention of these diseases is actively ongoing. Carotenoids are the major lipophilic pigments responsible for yellow-to-red colors in our diet, and the ingestion of certain carotenoids has been reported to prevent obesity. For example, β-carotene suppresses adipogenic differentiation of mouse preadipocyte line 3T3-L1 through its provitamin A activity. Fucoxanthin, a carotenoid found in brown algae, also has the similar effect via a different mechanism and is used as an active ingredient in foods with functional claims in Japan. In contrast, siphonaxanthin, a carotenoid found in some green algae such as Caulerpa lentillifera (commonly known as sea grape), exhibited stronger biological activities than other carotenoids in cell-based studies; it significantly suppressed adipogenic differentiation of 3T3-L1 cells even at low concentrations where β-carotene and fucoxanthin did not show inhibitory effects. However, its practical applications have not yet been realized. This review summarizes the studies on the anti-obesity effects of carotenoids and discusses the potential of siphonaxanthin as a novel functional food ingredient.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957284","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":"Insight of action mechanism of Astragaloside IV for relieving of cerebral ischemic injury in a rat model of middle cerebral artery occlusion reperfusion via proteomics and network pharmacology","authors":"Xin-Hua Zhu,&nbsp;Xin Yu,&nbsp;Xiang-Wen Kong,&nbsp;Yi Zhang,&nbsp;Si-Liang Jiang,&nbsp;Jun-Hong Chai,&nbsp;Jun Liang,&nbsp;Hai-Xue Kuang,&nbsp;Yong-Gang Xia","doi":"10.1007/s11418-025-01892-9","DOIUrl":"10.1007/s11418-025-01892-9","url":null,"abstract":"<div><p>Astragaloside IV (AS-IV) is the principal active component of <i>Astragalus membranaceus</i> (fisch.) Bge. var. <i>mongholicus</i> (Bge.) Hsiao. This study aims to explore action mechanism of AS-IV for relieving of cerebral ischemic injury in a rat model of middle cerebral artery occlusion reperfusion (MCAO) via proteomics and network pharmacology. Pharmacodynamics experiments showed that AS-IV could effectively alleviate MACO-induced cerebral infarction, preserve the structural integrity of neurons, and promote the formation of Sol bodies. In addition, TMT quantitative proteomics revealed differential proteins (DEPs), e.g., DGKQ, PPT1, Gnai3, Gnal, PLA2G4A, and Ppp2ca. These DEPs might be closely related to AS-IV for the therapeutic effects on ischemic stroke. In combination with network pharmacology, the PLA2G4A was further identified as key target protein of AS-IV ascribed to its involvement in the regulation of inflammatory mediators in the TRP pathway. Ultimately, in <i>vitro</i> validation demonstrated that AS-IV offers neuroprotective effects by targeting the PLA2G4A, reducing the release of arachidonic acid (AA) and COX-2, and facilitating Ca²⁺ inflow into cells. This study provided a scientific basis on development and application of AS-IV for treating ischemic stroke.</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 3","pages":"591 - 607"},"PeriodicalIF":2.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918960","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":"Tenacissoside G reverses paclitaxel resistance by inhibiting Src/PTN/P-gp signaling axis activation in ovarian cancer cells","authors":"Jiudong Hu,&nbsp;Yujie Hu,&nbsp;Xiangqi Zhang,&nbsp;Jingxian Zhang,&nbsp;Yangyun Zhou,&nbsp;Xiaohe Wang,&nbsp;Wenhui Wu,&nbsp;Junjun Chen,&nbsp;Yonglong Han","doi":"10.1007/s11418-025-01879-6","DOIUrl":"10.1007/s11418-025-01879-6","url":null,"abstract":"<div><p>Ovarian cancer (OC) is the most common malignant gynecologic tumor, with the highest mortality rate among female reproductive system cancers. Resistance to chemotherapy drugs, which often develops after long-term use, is a major cause of treatment failure. In recent years, traditional Chinese medicine has been widely used in the treatment of tumor for their advantages in improving the efficacy of chemotherapy and alleviating the toxic side effects. Tenacissoside G (Tsd-G), as one of the main active ingredients of <i>Marsdenia tenacissima,</i> exhibits anti-tumor effects. However, its impact on ovarian cancer is not well understood. To assess the role and mechanism of Tsd-G in reversing paclitaxel (PTX) resistance, the reversal fold of Tsd-G in combination with PTX on OC PTX-resistant (A2780/T) cells was determined using CCK-8 assay. The apoptosis level and migration ability of A2780/T cells after 24 h treatment with Tsd-G and PTX were assessed by Hoechst 33,342, flow cytometry, and wound healing assay. Western Blot and Src overexpression plasmid were used to explore the relationship between Src and PTX resistance. The relationship between Src expression and human OC was analyzed by gene expression database. The effect of Tsd-G on P-gp activity was detected by flow cytometry. Western blot and RT-PCR experiments were performed to detect the differences in mRNA and protein expression of Src/PTN/P-gp signaling axis to validate the mechanism of Tsd-G in reversing the resistance to PTX in ovarian cancer. The results showed that Tsd-G reverses PTX resistance in ovarian cancer cells by regulating cell proliferation, cell cycle, inducing apoptosis, and inhibiting migration. The mechanism might associate with the inhibition of Src expression and phosphorylation activation, which in turn inhibits the expression and activity of downstream PTN and P-gp. This study provides a new idea for the treatment of PTX-resistant OC patients and provides theoretical support for revealing the anti-ovarian cancer active ingredients in <i>Marsdenia tenacissima</i>.</p><h3>Graphical abstract</h3><p>Tsd-G reverses PTX resistance by inhibiting the Src/PTN/P-gp signaling axis and inducing PTX accumulation in ovarian cancer paclitaxel-resistant cells.</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 3","pages":"621 - 638"},"PeriodicalIF":2.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802147","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":"Inhibitory effects of reumycin produced by Streptomyces sp. TPMA0082 on virulence factors of Pseudomonas aeruginosa","authors":"Jiahao Zeng,&nbsp;Yohei Iizaka,&nbsp;Yasuhiro Ouchi,&nbsp;Kouharu Otsuki,&nbsp;Takashi Kikuchi,&nbsp;Wei Li,&nbsp;Yojiro Anzai","doi":"10.1007/s11418-025-01902-w","DOIUrl":"10.1007/s11418-025-01902-w","url":null,"abstract":"<div><p><i>Pseudomonas aeruginosa</i> is an opportunistic human pathogen that causes a wide range of infections. The increasing multidrug-resistance of <i>P. aeruginosa</i> poses a critical challenge for medical care. <i>P. aeruginosa</i> employs virulence factors and biofilms to establish infections in humans and protect itself from environmental stress or antibiotics. These factors are regulated by a quorum sensing mechanism involving multiple regulatory systems that act interdependently through signaling molecules. Therefore, interference with quorum sensing systems can suppress the pathogenicity of <i>P. aeruginosa</i>. In this study, quorum sensing inhibitors were explored from secondary metabolites derived from 111 strains of actinomycetes by targeting the <i>las</i> system, which is thought to be upstream of the quorum sensing cascade in <i>P. aeruginosa</i>. As a result, reumycin was isolated from the culture broth of <i>Streptomyces</i> sp. TPMA0082. Reumycin, a molecule containing a pyrimidotriazine ring, inhibited the binding of the autoinducer to the LasR receptor in the <i>las</i> system, thereby suppressing the production of <i>P. aeruginosa</i> virulence factors, including pyocyanin, rhamnolipids, elastase, motility, and biofilms, without affecting bacterial growth. Toxoflavin, a reumycin derivative with a methyl group at the N1 position, exhibited strong antibacterial activity. Fervenulin, a reumycin derivative with a methyl group at the N8 position, had a negative impact on the logarithmic growth phase of the bacteria and exhibited lower inhibitory activity against virulence factor production compared to reumycin. These findings suggest that the position and number of methyl groups attached to the pyrimidotriazine structure significantly influence its biological activity, exerting distinct effects on quorum sensing inhibition and antibacterial activity.</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 3","pages":"608 - 620"},"PeriodicalIF":2.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802199","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":"Processing reduces diester diterpenoid alkaloids content of fuzi products, resulting in reduced toxicity and modified bioactivities","authors":"Tian Xiang,&nbsp;Xiaozhou Yang,&nbsp;Xiaoyao Zhang,&nbsp;Haobo Yuan,&nbsp;Man Xu,&nbsp;Chenxuan Yang,&nbsp;Murtala Bindawa Isah,&nbsp;Chen Chen,&nbsp;Hao Han,&nbsp;Xiaoying Zhang","doi":"10.1007/s11418-025-01895-6","DOIUrl":"10.1007/s11418-025-01895-6","url":null,"abstract":"<div><p>Fuzi is a generic term for various processed products of the lateral roots of <i>Aconitum carmichaelii</i> Debeaux, with a long history of medicinal use including hypoglycemic, anti-inflammatory, and immunity-enhancing. However, the toxicity of Fuzi limits its widespread use. Different processing methods have been used to minimize toxicity and improve the medicinal properties of Fuzi. Three processed Fuzi products were prepared according to Chinese Pharmacopoeia and their chemical compositions were qualitatively and quantitatively analysed using UPLC-MS. The toxicity, antioxidant properties and bioactivity changes were assessed in <i>Caenorhabditis elegans</i>. A total of 99 compounds were preliminarily identified, and a subsequent multivariate analysis showed significant differences among the different processed products in terms of chemical compositions. The processing led to a significant loss of alkaloids, decrease in the contents of total polyphenols and flavonoids, and a decrease in antioxidant capacity while increasing the total polysaccharide and uronic acid contents in Yan Fuzi and Hei Shunpian as well as the content of monoester diterpenoid alkaloids in Hei Shunpian and Bai Fupian. Furthermore, the processed products prevented cold stress in <i>C. elegans</i>. In conclusion, processing altered the composition and reduced the toxicity of Fuzi and led to differences in the pharmacological activities of different processed Fuzi products. These results provide a theoretical basis for the in-depth pharmacological study and application of processed products of Fuzi.</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 3","pages":"695 - 705"},"PeriodicalIF":2.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802146","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 of the mechanism of Buyang Huanwu decoction in improving learning and memory impairment in Alzheimer's disease mice based on lipidomics","authors":"Jing Jiang,&nbsp;Kai Duo,&nbsp;Siyu Zhu,&nbsp;Yitong Wang,&nbsp;Hui Xue,&nbsp;Chengyu Piao,&nbsp;Yifan Ren,&nbsp;Xia Lei,&nbsp;Yafeng Zhang,&nbsp;Jianxin Liu,&nbsp;Lihong Yang,&nbsp;Ning Zhang","doi":"10.1007/s11418-025-01890-x","DOIUrl":"10.1007/s11418-025-01890-x","url":null,"abstract":"<div><p>In this study, a lipid disorder Alzheimer’s disease (AD) model was developed with high-fat diet and <span>d</span>-galactose injected intraperitoneally (HFD &amp; <span>d</span>-gal) to evaluate the activities of Buyang Huanwu Decoction (BYHWD) compared with donepezil hydrochloride. The learning and memory abilities of BYHWD were evaluated by Morris water maze test (MWM). The lipid levels in serum, histopathology, and immunohistochemistry of hyperphosphorylated tau protein in hippocampal neurons were conducted to prove the therapy effects of BYHWD. After the identification of constituents absorbed into the brain using LC–MS, UPLC-TQ-MS was employed to analyze endogenous lipid metabolites in the hippocampi of mice. Based on the validated differential markers identified through lipidomics analysis, we further substantiated potential therapeutic pathway of BYHWD through the application of molecular docking technology. The mechanism underlying BYHWD was subsequently confirmed by palmitic acid-injured HT22 cells. The results showed that BYHWD significantly improved the cognitive deficits and regulated the lipid levels of HFD &amp; D-gal mice. BYHWD also protected the neuronal cell condition of hippocampal neurons, increased the density of dendritic spines, and reduced the expression of P-tau. Lipidomics revealed that 41 differential lipid metabolites were retuned after BYHWD administration, and this change may be related to the PPARγ pathway. Calycosin-7-glucoside showed good interaction with PPARγ in vivo composition analysis. Calycosin-7-glucoside increased the mRNA expression levels of lipid metabolism-related enzymes and PPARγ, as well as the expression of PPARγ protein in vitro study. BYHWD activated the PPARγ pathway to induce peroxisome proliferation and regulated lipid metabolism disorders in the AD mice brain.</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 3","pages":"568 - 590"},"PeriodicalIF":2.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-025-01890-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802143","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}