查找使用阿拉丁产品的科研文献

Network pharmacology-based strategy to reveal the mechanism of pinocembrin against ovarian cancer

Wang Guanghui,Cheng Jianxiang,Yao Meizhen,Li Jing,Chen Ting,Zhang Jia,Du Wensheng,Chen Youguo

Ovarian cancer stands as the foremost cause of mortality among gynaecological diseases globally, characterized by high morbidity and mortality. Pinocembrin, a flavonoid from natural plant sources, exhibits diverse pharmacological properties. Despite its known pharmacological activities, its specific role in ovarian cancer treatment remains scarcely reported, and its precise molecular mechanism remains elusive. This study integrates network pharmacology and molecular docking techniques to explore pinocembrin’s potential mechanism in ovarian cancer treatment. The targets of pinocembrin were compiled from the several online databases. Ovarian cancer targets were identified using the GeneCards database, with common target genes determined by data aggregation. Protein–protein interactions were analysed using the STRING platform. Subsequent Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Molecular docking assessed the binding affinity between potential targets and active compounds. Finally, target validity was verified through in vitro experiments. We identified 163 potential pinocembrin targets for ovarian cancer treatment. GO and KEGG analyses revealed pinocembrin’s involvement in protein kinase activity, protein phosphorylation, protein kinase complexes and cancer pathways in ovarian cancer treatment. Molecular docking demonstrated strong binding affinity between pinocembrin and most potential target active sites. In vitro experiments suggested pinocembrin’s potential to induce apoptosis in ovarian cancer cells through the AKT1-mTOR signalling pathway. This study comprehensively elucidates pinocembrin’s potential targets and mechanisms against ovarian cancer, aiming to provide promising candidates for developing novel and effective alternative and/or complementary nutritional supplements for the clinical treatment of ovarian cancer.

Rehmanniae Radix Praeparata in Blood Deficiency Syndrome: UPLC-Q-TOF-MS Profiling, Network Pharmacology, and PI3K-AKT Activation

Ruxi Gao,Fanyi Wang,Xiang Liu,Chu Yuan,Guoshun Shan

This study investigated the therapeutic mechanism of Rehmanniae Radix Praeparata (RRP) in treating blood deficiency syndrome (BDS) through integrated chemical analysis and pharmacological validation. UPLC-Q-TOF-MS identified chemical components of Rehmanniae Radix (RR) and RRP, with network pharmacology analysis suggesting AKT1 and NOS3 in the PI3K-AKT pathway as potential therapeutic targets. Pharmacodynamic evaluations using ELISA, hematological analysis, histopathology, and immunohistochemistry demonstrated RRP’s efficacy in improving hematological parameters, energy metabolism, and organ pathology in BDS mice. Experimental validation via RT-qPCR and Western blot confirmed significant upregulation of AKT1 and NOS3 mRNA and protein expression following RRP treatment. The findings indicate that RRP alleviates BDS by activating the PI3K-Akt signaling pathway to modulate AKT1 and NOS3 expression, providing mechanistic insights into its therapeutic actions.

Modified Podophyllotoxin Phenoxyacetamide Phenylacetate Derivatives: Tubulin/AKT1 Dual-Targeting and Potential Anticancer Agents for Human NSCLC

Hongyan Lin,Dongxuan Ai,Qingqing Liu,Xinling Wang,Jiale Gao,Qingqing Chen,Lingyu Ruan,Yuheng Tao,Jian Gao,Liqun Wang

Cancer is a major disease threatening human health worldwide, among which non-small-cell lung cancer (NSCLC) is the most deadly. Clinically, almost all anticancer drugs eventually fail to consistently benefit patients due to serious drug resistance. AKT is a key effector of the PI3K/AKT/mTOR pathway, which is closely related to the occurrence, development, and drug resistance of tumors. Herein, we first designed and synthesized 20 kinds of novel hybrid molecules targeting both tubulin and AKT based on a podophyllotoxin (PPT) skeleton through computer-aided drug design. By CCK8 assay, we screened the compound D1-1 (IC50 = 0.10 μM) with the strongest inhibitory activity against H1975 cells, and its activity was 100 times higher than PPT (IC50 = 12.56 μM) and 300 times higher than gefitinib (IC50 = 32.15 μM). Affinity analysis results showed that D1-1 not only retained the tubulin targeting of PPT but also showed strong AKT targeting. Subsequent pharmacological experiments showed that D1-1 significantly inhibited the proliferation and metastasis of H1975 cells and slightly induced their apoptosis by inhibiting both tubulin polymerization and the AKT pathway activation. Collectively, these data demonstrate that the novel hybrid molecule D1-1 may be an excellent lead compound for the treatment of human NSCLC as a dual inhibitor of tubulin and AKT.

BPQDs@Lipo-YSA Nanoplatform Triggers Mitophagy via PRKN/AKT1 to Drive Immunogenic Cell Death in Lung Adenocarcinoma

Ai Li,Liu Zhijuan,Li Ran,Hu Ying,Li Yongxia

Background Lung adenocarcinoma, the most common type of non-small cell lung cancer (NSCLC), is a leading cause of cancer-related deaths globally due to its high incidence and treatment difficulty. Despite recent advancements in treatment methods, the prognosis for patients with advanced disease remains poor. Studies have shown that targeting mitophagy, the selective clearance of damaged mitochondria, can influence the sensitivity of cancer cells to treatment. Methods In this study, we designed and synthesized BPQDs@Lipo-YSA, a novel nanomaterial, aimed at specifically inducing mitophagy in lung adenocarcinoma cells. The nanomaterial was characterized using techniques such as transmission electron microscopy (TEM) and dynamic light scattering (DLS). The ability of BPQDs@Lipo-YSA to induce mitophagy was evaluated using Western blot, immunofluorescence, and flow cytometry. Additionally, in vitro and in vivo experiments were conducted to investigate the impact of BPQDs@Lipo-YSA on lung adenocarcinoma cells through the induction of immunogenic cell death (ICD). Results Experimental results showed that BPQDs@Lipo-YSA effectively induced mitophagy in lung adenocarcinoma cells by activating the PRKN/AKT1 pathway. More importantly, this induction of mitophagy significantly enhanced the cytotoxic effect on lung adenocarcinoma cells. In animal models, BPQDs@Lipo-YSA, by inducing ICD, markedly inhibited tumor growth and extended survival. Conclusions This study reveals the potential value of BPQDs@Lipo-YSA in lung adenocarcinoma treatment through the induction of mitophagy and ICD. This finding provides theoretical and technical support for the development of new therapeutic strategies for lung adenocarcinoma.

Effects of perfluoroundecanoic acid on the function of Leydig cells in adult male rats

Xiu Xin,Haiqiong Chen,Fuhong Tian,Jingjing Li,Haoni Yan,Yige Yu,Feifei Ma,Huitao Li,Yiyan Wang,Xiaoheng Li,Yang Zhu,Ren-shan Ge

Perfluoroundecanoic acid (PFUnA), a perfluorinated compound , has environmental persistence, bioaccumulation , and potential toxicity. However, its effect on Leydig cell function remains unclear. Rats (age of 56 days) were gavaged with 0 (corn oil), 0.1, 0.5, 1, or 5 mg/kg/day PFUnA for 28 days. PFUnA significantly reduced serum testosterone levels as low as 0.5 mg/kg. PFUnA markedly decreased Leydig cell number as low as 0.1 mg/kg. PFUnA markedly reduced transcript levels of Star and Insl3 in the testes at 1 mg/kg after adjusting to Leydig cell number. It also reduced their protein levels. PFUnA significantly decreased the phosphorylation of AKT1 and mTOR as low as 0.1 mg/kg and the phosphorylation of ERK1/2 at 1 mg/kg and the phosphorylation of AKT1, AKT2, ERK1/2, and mTOR in Leydig cells at various concentrations (0.01–10 μM) after 24 h of in vitro treatment. In conclusion, PFUnA inhibits Leydig cell function possibly via AKT/ERK1/2/mTOR signaling pathways.

Integrated Identification of Macrophage NF-κB, p38 MAPK and AKT1 Signalling as Candidate Targets of Zerumbone in Experimental Periodontitis

Characterised by progressive alveolar bone loss, periodontitis arises from immune dysregulation and is classified as a chronic inflammatory condition. Zerumbone (Zer) has anti-inflammatory properties; however, its mechanism within the periodontal context remains unclear. We investigated the therapeutic effects and potential molecular targets of Zer by integratingin vivoefficacy assessment (using male C57BL/6 mice), network pharmacology, molecular docking, and molecular dynamics simulations, together with analysis of public single-cell transcriptomic data, with mechanistic validation using RAW 264.7 macrophages stimulated with LPS. In vivo, Zer attenuated bone resorption, preserved collagen integrity, reduced the number of TRAP-positive osteoclasts, and mitigated inflammation without hepatorenal toxicity. Network pharmacology predictedNFKB1,MAPK14, andAKT1as potential core targets, while IL-17 pathway enrichment suggested the involvement ofIL17A; single-cell data localisedNFKB1/MAPK14/AKT1to macrophages and showed thatIL17Ais predominantly expressed in T cells. In vitro, Zer dose-dependently suppressed LPS-driven phosphorylation of NF-κB p65, p38 MAPK and AKT1, correlating with reduced pro-inflammatory cytokine release and an M1-to-M2 phenotypic shift. In vivo, Zer also reduced gingival IL-17A expression. However, as IL-17A is primarily produced by T cells and our in vitro experiments were conducted exclusively in macrophages, this observation remains correlative and does not establish a direct T-cell-mediated effect. Collectively, these findings suggest that Zer ameliorates periodontitis partly through suppression of macrophage NF-κB and p38 MAPK signalling, with reduced AKT1 phosphorylation observed alongside these effects; however, whether AKT1 causally contributes to these effects remains to be determined. In addition, the potential impact on T-cell-associated IL-17A responses warrants further investigation.

Natural product puerarin activates Akt and ameliorates glucose and lipid metabolism dysfunction in hepatic cells

Yunbing Shen,Shengnan Yang,Xueyan Hu,Man Zhang,Xiaoyao Ma,Zhihua Wang,Yuanyuan Hou,Gang Bai

Puerarin, one of the major isoflavonoid compounds isolated from Gegen, is widely used to treat glucose and lipid disorders. Identifying the mechanism of puerarin’s action against lipid and glucose metabolism dysfunction is very important for its application and development. Based on the structure of puerarin, different chemical probes were synthesized to capture and identify puerarin’s protein target. A membrane translocation assay was conducted to identify the interaction between puerarin and target proteins. The results show that puerarin targets the PH domain of Akt1, inhibits Akt1′s transmembrane effect and activates Akt1. Activated Akt1 improves the phosphorylation or activity of downstream proteins, such as GSK-3β and PDE3, and ultimately regulates glucose and lipid metabolism. Puerarin, as a dietary supplement, could target the PH domain of Akt1 to activate the insulin pathway and improve insulin resistance, thereby assisting in the regulation of glucose and lipid metabolism disorders.

Discovery of an AKT1-targeting compound from a traditional herbal formula for alcoholic liver disease via integrative computational and experimental approaches

Yang Shuxuan,Zou Caiting,Li Dexian,Lin Jingxin,Chen Qinghong,Chen Meilin,Wu Chuanghai,Hung Andrew,Liu Yanyan,Sun Xiaomin,Li Hong,Wang Qi,Zhao Xiaoshan

Background Alcoholic liver disease (ALD) poses a major global health challenge, with limited effective interventions. The Dampness-Heat Regulating Formula (DRF), a traditional Chinese herbal tea composed of nine edible medicinal herbs, has shown promise in mitigating alcohol-induced liver injury. This study aimed to identify its core active components and elucidate underlying mechanisms. Methods Active compounds were retrieved from multiple databases and screened using chemical similarity, target prediction, and ADMET filtering. Disease-related targets were identified through public transcriptomic datasets. Three machine learning algorithms—random forest, support vector machine, and LASSO—were used to prioritize therapeutic targets. High-throughput molecular docking and virtual screening were combined with untargeted metabolomics to identify candidate compounds. The interaction between oleanolic acid (OA) and AKT1 was further verified by cellular thermal shift assay (CESTA). In vitro and in vivo assays were conducted to validate hepatoprotective effects. Additionally, the content of OA in DRF was quantified by HPLC to assess the relevance of experimental dosing. Results A total of 690 candidate compounds and 33 ALD-associated targets were identified. AKT1 emerged as the top-ranked hub target. OA showed strong binding affinity to AKT1, and CESTA confirmed their direct interaction. Functional assays demonstrated that OA alleviated ethanol-induced damage in hepatocytes and zebrafish models. HPLC analysis confirmed that DRF contained physiologically relevant concentrations of OA, supporting the translational relevance of the selected doses. Conclusion This study reveals a potential AKT1-centered mechanism through which DRF protects against ALD and identifies oleanolic acid as a bioactive compound with dual computational and experimental validation. It offers a scientific basis for integrating traditional herbal formulas with modern drug discovery approaches in the prevention of alcohol-related liver injury.

Berbamine improves behavioral impairments in Huntington's disease mice models through inhibiting Src/AKT1/NFκB signaling pathway and attenuating Src-mediated mitophagy suppression

Chunling Yuan,Li Zheng,Hongxia Hu,Xue Cheng,Peng Liu

Background Investigate the effects of berbamine (BBM) on alleviating motor and cognitive impairment in animal models of Huntington's disease (HD). Methods Intraperitoneal injection of 3-nitropropionic acid (3-NP) mice and B6-hHTT130-N transgenic mice were used as the HD models. We evaluated the anti-HD effect of BBM through behavioral experiments and employed molecular biological techniques, network pharmacology analysis, to test the potential mechanisms. Results BBM improved motor and cognitive impairment in 3-NP-injected and B6-hHTT130-N mice. BBM improved pathological damage in the brain, reduced the expression of mHTT in B6-hHTT130-N mice. BBM increased the ATP and mtDNA content, attenuated PINK1/Parkin-mediated mitophagy suppression. Furthermore, network pharmacology analysis, molecular docking and CETSA identified two targets: Src and AKT1. By using the Src inhibitor KX2–391, AKT inhibitor MK-2206 and NFκB inhibitor QNZ, we found that BBM showed a similar experimental results to Src inhibitor in Q74 plasmid transfected BV2 cells. BBM could inhibit the Src/AKT1/NFκB/NLRP3 signaling pathway-mediated neuroinflammation, and enhance PINK1/Parkin expression may through inhibiting Src. Conclusion BBM ameliorates motor and cognitive impairments in HD model mice through inhibition of neuroinflammation and mHTT expression, maintenance of mitochondrial function, which was mediated by inhibiting Src/AKT1/NFκB signaling pathway and attenuating Src-mediated mitophagy suppression.

Friedelin and 6-methoxyflavone from Imperata cylindrica ameliorate APAP-induced liver injury by activating AKT1 to suppress Caspase-3/GSDME-mediated pyroptosis

Pingting Wu,Weilai Chen,Jie Li,Jiayi Xing,Haote Wu,Jingyang Tong,Ping Chen,Haibin Tong,Yongping Chen,Chenwei Pan

Acetaminophen (APAP) overdose causes acute liver injury (ALI) by triggering regulated hepatocyte death. While Imperata cylindrica (Imperatae Rhizoma) (IR) is used in traditional medicine for its hepatoprotective effects, its active compounds and their capacity to modulate this pyroptotic switch remain unknown. In the present study, friedelin (FRI) and 6-methoxyflavone (6-METH) were identified as the principal active compounds of IR, and their protective effects against APAP-induced ALI were evaluated in vivo and in vitro. The results showed that both FRI and 6-METH significantly ameliorated APAP-induced liver injury and reduced hepatocyte death. Mechanistically, their hepatoprotective effects were associated with AKT1-dependent activation of the PI3K/AKT pathway, accompanied by suppression of Caspase-3/ Gasdermin E (GSDME) signaling and attenuation of apoptosis and pyroptosis. Moreover, pharmacological inhibition or genetic silencing of AKT1 markedly weakened these protective effects. Taken together, these findings suggest that FRI and 6-METH are major hepatoprotective constituents of IR and that modulation of the AKT1-mediated Caspase-3/GSDME pathway may contribute to their protective actions against APAP-induced ALI. These findings validate its active compounds as promising therapeutic leads for ALI.

Sini San ameliorates lipid metabolism in hyperprolactinemia rat with liver-depression

Weidong Xu,Shasha Tian,Guanqun Mao,Yu Li,Hua Qian,Wenhua Tao

Sini San (SNS) is used to treat liver depression and is applied in both food and herbal medicine. Hyperprolactinemia (HPRL) is a common endocrine disorder, and patients with HPRL are usually associated with depressive symptoms. However, whether SNS is effective in treating HPRL combined with liver depression and its underlying mechanisms are unknown. We applied network pharmacology and molecular docking to predict the mechanism of SNS for the treatment of liver-depressed HPRL. Therapeutic effects were validated in animal models and cells. Metabolomics was also used to evaluate the effect of SNS on liver-depressed HPRL. Network pharmacology and molecular docking analysis showed that AKT1, TNF and IL6 were the key targets, and SNS improved depressive behaviors, regulated sex hormone levels, and improved ovarian morphology. Combined network pharmacology and metabolomics analyses showed that SNS could act by regulating lipid metabolism. In addition, SNS significantly reduced the release of prolactin (PRL) in rat pituitary tumor MMQ cells. Overall, SNS can significantly treat HPRL liver depression at both animal and cellular levels, and effectively alleviate the related symptoms by regulating lipid metabolism. AKT1, TNF and IL6 may be key targets.

Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation

Wang Yuan-chun,Hui Jian-rong,Xiao Gang,Ma Qiao-lin

Objective To investigate the mechanism of the effect of Astragalus membranaceus ( A. membranaceus ) on lung adenocarcinoma at the molecular level to elucidate the specific targets according to the network pharmacology approach. Methods The active components of A. membranaceus and their potential targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database. Lung adenocarcinoma-associated genes were acquired based on GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGKB, and Therapeutic Targets databases. The PI3K/AKT signaling pathway-related genes were obtained using Reactome portal. Networks of “ingredient-target” and “ingredient-target-pathway-disease” were constructed using the Cytoscape3.6.0 software. The relationships among targets were analyzed according protein-protein interaction (PPI) network. Finally, molecular docking was applied to construct the binding conformation between active ingredients and core targets. Cell counting kit 8 (CCK8) and Western blot assays were performed to determine the mechanism of the key ingredient of A. membranaceus . Results A total of 20 active components and their 329 targets, and 7,501 lung adenocarcinoma-related genes and 130 PI3K/AKT signaling pathway-related genes were obtained. According to Venn diagram and PPI network analysis, 2 mainly active ingredients, including kaempferol and quercetin, and 6 core targets, including TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR, were identified. The two important active ingredients of A. membranaceus , kaempferol and quercetin, exert the therapeutic effect in lung adenocarcinoma partly by acting on the 6 core targets (TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR) of PI3K/AKT signaling pathway. Expressions of potential targets in lung adenocarcinoma and normal samples were analyzed by using UALCAN portal and found that ERBB2 was overexpressed in lung adenocarcinoma tissues and upregulation of it correlated with clinicopathological characteristics. Finally, quercetin repressed viabilities of lung adenocarcinoma cells by targeting ERBB2 on PI3K/AKT signaling confirmed by CCK8 and Western blot. Conclusion Our finding unraveled that an active ingredient of A. membranaceus , quercetin, significantly inhibited the lung adenocarcinoma cells proliferation by repressing ERBB2 level and inactivating the PI3K/AKT signaling pathway.