Combinatorial chemistry & high throughput screening最新文献

{"title":"Exploring the Therapeutic Potential of Plantaginis Herba in Treating Salt-Sensitive Hypertension-Induced Renal Injury: Network Pharmacology Analysis and Experimental Verification.","authors":"Ya Zhong, Zhongxin Sha, Jinxin Hu, Jie Zhang, Zhenqiu Yu","doi":"10.2174/0113862073412660251122070855","DOIUrl":"https://doi.org/10.2174/0113862073412660251122070855","url":null,"abstract":"<p><strong>Introduction: </strong>Plantaginis Herba (PH) is a traditional Chinese herb with broad pharmacological effects and has been used to treat hypertension. Salt-sensitive hypertension (SS-HT) is characterized by elevated blood pressure due to a high-salt diet and sodium intake. This study investigates the role and molecular mechanisms of PH in SS-HT-induced renal injury using network pharmacology and in vivo experiments.</p><p><strong>Methods: </strong>The components of PH and potential therapeutic targets were identified through network pharmacology. The protein-protein interaction (PPI) network and Herb-CompoundsTargets-Disease-Pathway network were established. GO and KEGG enrichment analyses were performed using DAVID and bioinformatics tools. Active compounds were determined by ultraperformance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS). A SS-HT model was established using male Dahl/SS rats given a high-salt diet, and then treated with lowand high-dose PH, as well as hydrochlorothiazide (HCTZ), upon which kidney injury, urine sodium metabolism-related factors, and PI3K/AKT/Nedd4-2/γ-ENaC pathway-related proteins levels were assessed using histopathological staining, ELISA, and Western blotting.</p><p><strong>Results: </strong>Ninety-nine overlapping genes were identified between PH and SS-HT, with AKT1 highlighted as a hub target in the PPI network. The contents of dinatin, baicalin, baicalein, 6-OHluteolin, β-sitosterol, and stigmasterol in the PH extracts were 1.880, 2.973, 0.210, 1.797, 385.400, and 38.320 ng/mg, respectively. KEGG identified the PI3K-Akt signaling pathway as a core signaling pathway. In vivo experiments showed that PH could improve blood pressure and urinary sodium metabolism, ameliorate kidney histopathological injury, and inhibit apoptosis. Furthermore, PH increased p-PI3K/PI3K, p-AKT/AKT, and Nedd4-2 expression while inhibiting γ-ENaC expression, thereby improving kidney injury and sodium excretion function in SS-HT rats.</p><p><strong>Discussion: </strong>PH contains multiple bioactive compounds and exerts its effects through multiple targets and pathways, effectively alleviating SS-HT and ameliorating pathological kidney damage, with an efficacy comparable to that of hydrochlorothiazide. PH improves urinary sodium metabolism and mitigates renal injury in SS-HT rats via the PI3K/AKT/Nedd4-2/γ-ENaC pathway. Although PH demonstrates potential as a therapeutic agent for SS-HT, the key functional components in PH and the mechanism by which Nedd4-2 participates in the degradation of γENaC remain to be further studied.</p><p><strong>Conclusion: </strong>PH ameliorates SS-HT-induced renal injury by regulating sodium metabolism and renal function, and by activating the PI3K/AKT/Nedd4-2/γ-ENaC pathway.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307252","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":"Herbal Gargle for Dry Mouth and Care: In vitro and Ex vivo Evaluations.","authors":"Evren Algın Yapar, Ebrar Inal, İmren Esentürk-Güzel, Bilge Ahsen Kara, Fatıma Nur Yılmaz, Cemre Özkanca, Luceyn Abdo, Meryem Sedef Erdal, Sibel Döşler, Murat Kartal","doi":"10.2174/0113862073411825251212024407","DOIUrl":"https://doi.org/10.2174/0113862073411825251212024407","url":null,"abstract":"<p><strong>Introduction: </strong>The current study aimed to design an ex vivo experimental method, in combination with in vitro analysis, to measure and evaluate sheep tongue dryness and wetness, which was used to assess the ex vivo efficacy of herbal gargle formulas for dry mouth/xerostomia. The test method was applied to the herbal gargle that was successfully designed in the first part of our study, which demonstrated good physicochemical characteristics, stability, antimicrobial efficacy, and safety as proven by in vitro gingival fibroblast cell studies.</p><p><strong>Methods: </strong>In vitro analysis and an ex vivo sheep tongue method, based on both gravimetric and texture analysis, were applied to the herbal gargle formula. For gravimetric analysis, the sheep tongues were weighed before and after being placed in an oral cavity mimic chamber. The adhesiveness of the sheep tongues was then measured using texture analysis.</p><p><strong>Results: </strong>In vitro evaluations and the ex vivo sheep tongue model showed that the herbal gargle formulation decreased tongue adhesivity while exhibiting the highest liquid retention capacity. The formula, which included 2% cinnamon leaf oil, 4% hazelnut oil, and a 0.5% CMC solution as the active ingredients, demonstrated strong ex vivo wetting ability with high liquid retention.</p><p><strong>Discussion: </strong>The results of both the in vitro evaluations and the ex vivo sheep tongue model confirmed that the herbal gargle formulation reduced tongue adhesivity and provided high liquid retention capacity. The formulation containing 2% cinnamon leaf oil, 4% hazelnut oil, and 0.5% CMC showed strong ex vivo wetting performance.</p><p><strong>Conclusion: </strong>In conclusion the herbal gargle formula, which demonstrated good physicochemical characteristics, stability, antimicrobial activity against oral pathogens, and safety for oral epithelial cells, strengthened its overall performance through successful ex vivo sheep tongue results, showing high liquid retention and low adhesiveness. These findings support the wettability potential of the investigated formula.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307233","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":"KMT2A Histone Methyltransferase Contributes to Intrahepatic Cholangiocarcinoma Cell Growth by Promoting JAK2 Transcriptional Activation.","authors":"Zaihua Yan, Mingxu Da","doi":"10.2174/0113862073422953251103073538","DOIUrl":"https://doi.org/10.2174/0113862073422953251103073538","url":null,"abstract":"<p><strong>Introduction: </strong>Intrahepatic cholangiocarcinoma (ICC) is known for its aggressive behavior and poor prognosis, but the role of dysregulated KMT2A in this cancer is not well understood. The study aimed to determine whether KMT2A functions as an oncogene in the development of ICC.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) provided the expression profiles of KMT2A in CHOL, which were then validated with clinical ICC samples from the Human Protein Atlas (THPA). The biological function of KMT2A was evaluated using plate colony formation and CCK8 assays. A joint analysis of public data, CHIP-PCR, Western Blotting, and RT-qPCR was carried out to provide mechanistic insights.</p><p><strong>Results: </strong>The expression levels of KMT2A were notably elevated in tumor samples compared to healthy samples. When KMT2A was overexpressed in ICC cells, cell proliferation was significantly enhanced, while its knockdown resulted in the opposite outcome. Furthermore, KMT2A elevated H3K4me3 in the JAK2 promoter region, thereby promoting JAK2 expression. It was found that activating JAK2/STAT3 could lessen the suppression of ICC proliferation caused by KMT2A knockdown.</p><p><strong>Discussion: </strong>In this study, a series of experiments was conducted. First, through public databases, we discovered that KMT2A expression was significantly higher in intrahepatic cholangiocarcinoma than in normal tissue. Furthermore, KMT2A promoted the proliferation of ICC cells. Finally, our findings indicate that KMT2A exerts its function, at least in part, by activating the JAK2/STAT3 signaling pathway via enhanced H3K4 trimethylation and increased JAK2 transcription.</p><p><strong>Conclusion: </strong>KMT2A was significantly upregulated in intrahepatic cholangiocarcinoma and elevated H3K4me3 levels at the JAK2 promoter, leading to higher JAK2 expression and activation of the JAK2/STAT3 pathway, which, in turn, stimulated ICC cell proliferation. This study offers novel insights into the potential of KMT2A as both a prognostic biomarker and therapeutic target for intrahepatic cholangiocarcinoma.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307276","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":"A phase I, randomized, dose-escalation clinical trial of the anti-IgE humanized monoclonal antibody LP-003 in healthy subjects.","authors":"Jinhong Li, Xiaoming Zhu, Heng Liu, Jie Yang, Cuicui Han, Feng Yan, Qingyu Wei","doi":"10.2174/0113862073484282260617132549","DOIUrl":"https://doi.org/10.2174/0113862073484282260617132549","url":null,"abstract":"<p><strong>Introduction: </strong>Immunoglobulin (Ig) E is crucial in driving inflammatory responses that lead to clinical symptoms of atopy. LP-003, a humanized Ig G1 kappa monoclonal antibody, blocks the binding of human IgE to the FcεRI receptor and was developed for the treatment of uncontrolled atopy. In this phase I trial, a randomized, double-blind, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) study was performed, and the safety, tolerability, pharmacokinetics (PK), and immunogenicity of LP-003 were assessed in healthy subjects.</p><p><strong>Methods: </strong>The study consisted of two parts: the SAD component and the MAD component. In the SAD study, five dose cohorts were planned (0.3/1.0/3.0/6.0/10.0 mg/kg). In the MAD study, two dose cohorts (2.0/4.0 mg/kg) were planned.</p><p><strong>Results: </strong>Most treatment-emergent adverse events (TEAEs) were mild or moderate, and their incidence was comparable between the LP-003 and placebo groups. The serum LP-003 concentration and PK exposures proportionally increased with dose level ranging from 0.3-10.0 mg/kg in SAD study and 2.0-4.0 mg/kg in MAD study, resulting in a prolonged serum half-life of ~70 days. The incidence of anti-drug antibodies (ADAs) was 12.5% in both SAD and MAD studies, showing no clear correlation with the dose or impact on safety.</p><p><strong>Conclusion: </strong>LP-003 demonstrated a favorable safety profile and a superior PK advantage characterized by an extended half-life, supporting its development as a long-acting therapeutic option for allergic conditions.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307197","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":"Fritillaria thunbergii Extracts Suppress Hepatocellular Carcinoma Proliferation and Metastasis via mTOR Signaling Pathways.","authors":"Qiaoxiu Tan, Qinhong Meng, Guanping Chen, Feifei He","doi":"10.2174/0113862073421780251224111026","DOIUrl":"https://doi.org/10.2174/0113862073421780251224111026","url":null,"abstract":"<p><strong>Introduction: </strong>Fritillaria thunbergii exhibits diverse medicinal properties, including anti-inflammatory and anticancer effects. Despite extensive research on F. thunbergii, its molecular mechanisms in liver cancer treatment remain elusive. This study aimed to elucidate the anticancer properties of an F. thunbergii alcohol extract (FAE) through a combination of in vitro and in vivo experiments.</p><p><strong>Methods: </strong>The effects of FAE on Huh7 and Hep3B cells were assessed in vitro and in vivo. Cell viability, migration, and invasion were determined using CCK-8, scratch wound healing, and transwell assays, respectively. Protein levels of mTOR pathway components (p-mTOR, mTOR) and cell cycle regulators (Cyclin D1, CDK4) were analyzed by western blotting. In vivo antitumor efficacy was evaluated in a xenograft model, with tumor tissues examined by HE staining and immunohistochemistry.</p><p><strong>Results: </strong>FAE exhibited potent antitumor activity against hepatocellular carcinoma in vitro and in vivo, without apparent cytotoxicity. It dose- and time-dependently inhibited cancer cell viability, migration, and invasion.</p><p><strong>Discussion: </strong>FAE treatment concurrently downregulated proliferative markers (Cyclin D1, CDK4) and suppressed mTOR activation, indicating the involvement of this key pathway in its mechanism of action. These findings collectively suggest that FAE has considerable potential as a therapeutic agent for the treatment of hepatocellular carcinoma.</p><p><strong>Conclusion: </strong>These findings collectively suggest that FAE possesses considerable potential as a therapeutic agent for hepatocellular carcinoma treatment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307254","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":"Epithelial Duox2 Drives Chronic Colitis-Associated Fibrosis via the NLRP3-IL-33-Mast Cell Axis.","authors":"Zhixiong Chen, Juanmin Yang, Zhigang He","doi":"10.2174/0113862073478558260523170837","DOIUrl":"https://doi.org/10.2174/0113862073478558260523170837","url":null,"abstract":"<p><strong>Introduction: </strong>Intestinal fibrosis is a common and serious complication of chronic inflammatory bowel disease (IBD) associated with stricture and obstruction. Although oxidative stress has been associated with IBD, how Duox2, the major source of ROS in gut epithelium, promotes fibrosis remains unknown. The goal of our study is to determine the role of Duox2 in IBD fibrosis.</p><p><strong>Methods: </strong>GEO datasets were analyzed using bioinformatics to find the main pathogenic factors. AOM/DSS-induced chronic colitis mouse model was established to assess fibrosis and Duox2 expression. Adeno-associated virus (AAV)-shRNA was employed to block Duox2 in vivo. In vitro, the potential signaling pathways were further explored by molecular and cell functional analyses.</p><p><strong>Results: </strong>RNA sequencing combined with in vivo validation showed that Duox2 is markedly upregulated in the colonic epithelium of mice with chronic colitis and fibrosis. The in vivo knockdown of Duox2 mitigated the colonic shortening and decreased collagen content, fibrosis markers, and MDA levels. Epithelial Duox2 upregulation induced NLRP3 inflammasome activation and IL-33 release. Paracrine IL-33 mobilized and activated mast cells, resulting in profibrotic factor release and epithelial migration. Addition of IL-33 neutralizing antibody in the co-culture model attenuated mast cell activation and fibrosis-promoting effects.</p><p><strong>Discussion: </strong>Collectively, our data indicate that Duox2 or the downstream IL-33 pathway is a potential therapeutic strategy for intestinal fibrosis.</p><p><strong>Conclusion: </strong>Our findings identify a Duox2-NLRP3-IL-33-Mast Cell axis in chronic colitisassociated fibrosis. Epithelial Duox2 activation induces NLRP3-mediated IL-33 release, which promotes mast cell infiltration.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276404","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":"Arctigenin Induces Mitochondrial Apoptosis in Ovarian Cancer Cells by Downregulating Bcl2L12 Expression.","authors":"Ying Yang, Peng Cui, Weiyan Chen, Qun Wang, Tianmin Ji, Jiaxin Wang, Jiao Zhao, Nan Song","doi":"10.2174/0113862073373659260101094951","DOIUrl":"https://doi.org/10.2174/0113862073373659260101094951","url":null,"abstract":"<p><strong>Introduction: </strong>Ovarian cancer remains one of the most lethal gynecological malignancies because of late diagnosis, drug resistance, and limited treatment efficacy. This study explored the anti-apoptotic role of BCL2-like protein 12 (BCL2L12) and whether arctigenin induces apoptosis by targeting BCL2L12.</p><p><strong>Methods: </strong>SK-OV-3 and OVCAR-3 ovarian cancer cells were subjected to BCL2L12 knockdown or overexpression. Cell viability, proliferation, and apoptosis were evaluated by CCK-8, colony formation, and Annexin V/PI flow cytometry. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were assessed using JC-1 and DCFH-DA staining, respectively, and apoptosis- and autophagy-related proteins were examined by western blotting. Public databases (TCGA, GTEx, CSIOVDB, Kaplan-Meier Plotter) were used to evaluate BCL2L12 expression and prognosis.</p><p><strong>Results: </strong>BCL2L12 was markedly upregulated in ovarian cancer and correlated with advanced stage and poor survival. Silencing BCL2L12 reduced cell growth, disrupted mitochondrial homeostasis, increased ROS accumulation, and enhanced caspase-3/7-dependent apoptosis while inhibiting autophagy. Arctigenin inhibited cell proliferation, downregulated BCL2L12, and induced mitochondrial apoptosis accompanied by ROS elevation and caspase-3/7 activation, whereas BCL2L12 overexpression attenuated these effects.</p><p><strong>Discussion: </strong>BCL2L12 acts as an anti-apoptotic factor in ovarian cancer by maintaining mitochondrial integrity and suppressing caspase-3/7 activation. Arctigenin overcomes this survival advantage by suppressing BCL2L12 and triggering mitochondrial apoptosis. Limitations include validation only in two cell lines and the lack of direct enzymatic assays for caspase-3/7 activity.</p><p><strong>Conclusion: </strong>Arctigenin induces mitochondrial apoptosis in ovarian cancer by downregulating BCL2L12, supporting its potential as a low-toxicity therapeutic candidate.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276283","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":"lncRNA-miRNA-mRNA Network Analysis and Downstream Proteins Reveal the Mechanism of Bushen Huatan Prescription in the Treatment of Polycystic Ovary Syndrome.","authors":"Wenting Xu, Lingli Shi, Xiuqin Tang, Rong Wang, Lili Zhu, Lijuan Cui, Lihong Wang","doi":"10.2174/0113862073435496260101112553","DOIUrl":"https://doi.org/10.2174/0113862073435496260101112553","url":null,"abstract":"<p><strong>Introduction: </strong>Polycystic Ovary Syndrome (PCOS) is a prevalent reproductive endocrine disorder. The underlying mechanisms, particularly the role of the long non-coding RNA (lncRNA)- miRNA-mRNA network, remain incompletely understood. The Bushen Huatan (BSHT) prescription shows clinical efficacy in treating PCOS, but its active components and their regulatory effects on this network are largely unknown.</p><p><strong>Method: </strong>Active components of the BSHT extract were analyzed using UHPLC-HR-MS. RNA and lncRNA sequencing were performed to identify differentially expressed lncRNAs, miRNAs, and mRNAs in PCOS rat models. A potential competing endogenous RNA (ceRNA) network was constructed and subsequently validated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and qRT-PCR. Finally, Western blot analysis was used to evaluate the effect of BSHT on the expression of downstream insulin receptor proteins and signaling pathway proteins.</p><p><strong>Results: </strong>UHPLC-HR-MS identified 503 active ingredients in the BSHT extract. Compared to controls, PCOS rats exhibited 1181 differentially expressed lncRNAs and 2696 mRNAs. BSHT treatment significantly altered the expression of 336 lncRNAs and 678 mRNAs, and qRT-PCR showed that lncRNA XLOC-018280 expression was significantly downregulated by approximately 4-fold (P<0.01) in the MC group compared to the NC group, and this was significantly reversed by BSHT treatment. Western blot showed that INSR, IRS-1, IRS-2, PI3K, and p-AKT were differentially expressed.</p><p><strong>Conclusion: </strong>The Bushen Huatan prescription alleviates the endocrine and metabolic disorders of PCOS by regulating the lncRNA-miRNA-mRNA network and affecting the expression of downstream proteins INSR, IRS-1, IRS-2, PI3K, and p-AKT.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276391","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":"Mechanistic Study on the Treatment of Acute Lung Injury with Qingwen Baidu Decoction based on NLRP3 Inflammasome Signaling Pathway.","authors":"Jinhui Feng, Xiangzheng Mao, Wenting Wang, Ke Yang, Sha Li, Bin Wang, Jiping Liu, Yongheng Shi, Hao Wei, Chuan Wang, Peng Zhao, Taiwei Dong, Xu Chao, Shuanlao Yang, Guoquan Wang","doi":"10.2174/0113862073387330251111021249","DOIUrl":"https://doi.org/10.2174/0113862073387330251111021249","url":null,"abstract":"<p><strong>Introduction: </strong>Qingwen Baidu Decoction (QWBD), a classical traditional Chinese medicine formula, has demonstrated clinical efficacy in managing acute lung injury (ALI). However, the precise mechanisms underlying its protective effects remain poorly characterized.</p><p><strong>Methods: </strong>Major bioactive constituents of QWBD were identified through high-performance liquid chromatography (HPLC). Lipopolysaccharide (LPS)-induced in vivo and in vitro inflammatory models were established to evaluate therapeutic outcomes. Pulmonary edema severity was assessed via lung wet-to-dry weight ratio (W/D), while histopathological alterations were examined through hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). Myeloperoxidase (MPO) activity and inflammatory cytokine levels were quantified to determine neutrophil activation and inflammatory responses. Mechanistic insights were obtained through immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) targeting the NLRP3 inflammasome pathway.</p><p><strong>Results: </strong>HPLC analysis identified four principal bioactive components in QWBD. Treatment significantly attenuated pulmonary edema, ameliorated alveolar structural damage, and restored ultrastructural integrity of type II pneumocytes in ALI rats. QWBD significantly suppressed MPO activity and reduced pro-inflammatory cytokine levels compared to the LPS-treated group. IHC/IF revealed potent inhibition of cysteine-aspartic protease-1 (Caspase-1) and NOD-like receptor protein 3 (NLRP3) expression, while WB confirmed downregulation of NLRP3 inflammasome- associated proteins.</p><p><strong>Discussion: </strong>QWBD alleviates ALI by inhibiting NLRP3 inflammasome activation and upstream regulators, thereby attenuating pro-inflammatory cytokine maturation. Its multi-component composition confers advantages over single-target agents while potentially avoiding the broad immunosuppression associated with dexamethasone. Clinical validation of its therapeutic potential remains warranted.</p><p><strong>Conclusion: </strong>QWBD protects against ALI by implying NLRP3 inflammasome suppression, demonstrating promise as a multi-targeted therapy for inflammatory lung disorders.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270625","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":"Elucidating the Potential Anti-asthmatic Mechanism of Aster tataricus by Combining Network Pharmacology with Experimental Validation in a Murine Model.","authors":"Yun Zang, Jia-Ning Zhang, Si-Qi Yang, Yan Wang, Hui-Feng Li, Jin-Yan Tan, Rong-Li You, Yi Zhang, Ying-Li Wang, Yan-Gang Cheng","doi":"10.2174/0113862073449907260515062236","DOIUrl":"https://doi.org/10.2174/0113862073449907260515062236","url":null,"abstract":"<p><strong>Introduction: </strong>Asthma is a prevalent chronic airway disease with unmet therapeutic needs. Aster tataricus L. f. (AT), a traditional herbal medicine used for respiratory conditions, shows potential for asthma treatment; however, its underlying pharmacological mechanisms remain largely unexplored. This study aimed to systematically investigate the potential therapeutic effects of AT against asthma and elucidate its underlying molecular mechanisms by integrating network pharmacology prediction, molecular docking validation, and in vivo experimental confirmation.</p><p><strong>Methods: </strong>To evaluate the anti-asthmatic potential of AT, an Ovalbumin (OVA)-induced murine model of allergic airway inflammation was employed. Pathological alterations in airway inflammation and remodeling were assessed via histochemistry (H&E, PAS, Masson's trichrome). Concurrently, the levels of key cytokines (IL-4, IL-5, IL-10, IL-13, IFN-γ) in Bronchoalveolar Lavage Fluid (BALF) were quantified by Enzyme-Linked Immunosorbent Assay (ELISA). Network pharmacology predictions and molecular docking analyses were integrated to identify potential targets and pathways, which were subsequently validated through Immunohistochemistry (IHC) and Immunofluorescence (IF).</p><p><strong>Results: </strong>In a murine model of allergic airway inflammation, AT treatment significantly alleviated airway inflammation and fibrosis. This therapeutic effect was characterized by a distinct shift in the BALF cytokines: a reduction in the levels of IL-4, IL-5, and IL-13, coupled with an elevation in IL-10 and IFN-γ. This shift was accompanied by diminished inflammatory cell infiltration and collagen deposition in lung tissue. Network pharmacology predicted core targets (e.g., EGFR, STAT3, TLR4, MMP9) and key pathways (e.g., PI3K-Akt and JAK-STAT). Experimental validation confirmed that AT downregulated the expression of these key targets. Furthermore, molecular docking revealed stable binding between active constituents in AT (such as Aster saponin F) and the core targets, suggesting a potential mechanism of action.</p><p><strong>Discussion: </strong>This study demonstrates the potential anti-asthmatic effects of AT in a murine model of allergic airway inflammation. The integrated research strategy reveals its multi-component synergistic mechanism of action.</p><p><strong>Conclusions: </strong>AT exerts potentially anti-asthmatic effects by means of multi-component and multi-target mechanisms, with the regulation of the PI3K-Akt and JAK-STAT pathways. This study elucidates the anti-asthmatic mechanism of AT and provides scientific evidence supporting its clinical application for asthma treatment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270689","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}