Jianwei Yu, Xueqiong Deng, Xueqin Lin, Li Xie, Sisi Guo, Xiaoliang Lin, Dong Lin
{"title":"DST regulates cisplatin resistance in colorectal cancer via PI3K/Akt pathway.","authors":"Jianwei Yu, Xueqiong Deng, Xueqin Lin, Li Xie, Sisi Guo, Xiaoliang Lin, Dong Lin","doi":"10.1093/jpp/rgae104","DOIUrl":"https://doi.org/10.1093/jpp/rgae104","url":null,"abstract":"<p><strong>Objectives: </strong>Dystonin (DST), a potential tumor suppressor gene, plays a crucial role in regulating cancer cell proliferation and resistance to chemotherapy. However, DST's specific role in colorectal cancer (CRC) has not been thoroughly investigated, and this study aims to elucidate its molecular role in modulating cisplatin (DDP) resistance in CRC.</p><p><strong>Methods: </strong>DST expression was analyzed in CRC tumors, DDP-resistant CRC tissues, paracancer tissues, and normal tissues. Lentiviral overexpression and shRNA knockdown were conducted in advanced CRC and DDP-resistant cell lines to assess cell viability, apoptosis, invasion, migration, proliferation, and angiogenesis. Xenograft mouse models studied DST's impact on CRC tumor growth and DDP resistance in vivo.</p><p><strong>Results: </strong>DST expression was significantly reduced in CRC tumor and DDP-resistant CRC tissues compared to paracancer and normal tissues (P < .001). Upregulating DST inhibited CRC and DDP-resistant cell viability, proliferation, invasion, and migration while promoting apoptosis. DST overexpression also reduced angiogenesis and attenuated DDP-induced cytotoxicity in CRC cells. Mechanistically, DST upregulation suppressed DDP resistance in CRC cells via the PI3K/Akt signaling pathway. DST upregulation reduced CRC tumor growth and mitigated DDP resistance, in vivo.</p><p><strong>Conclusion: </strong>DST plays a crucial role in limiting CRC progression and overcoming DDP resistance, suggesting potential for targeted CRC therapies.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468354","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}
Ling Zhu, Beijia Wang, Pingping Li, Gangli Cheng, Su Bu, Sijie Bian, Xiaoting Qiu, Jian Liu, Xingxing Huo
{"title":"Improvement of primary Sjögren's syndrome salivary gland function by Xinfeng capsule and its effect on EGR1-STAT3 signaling pathway.","authors":"Ling Zhu, Beijia Wang, Pingping Li, Gangli Cheng, Su Bu, Sijie Bian, Xiaoting Qiu, Jian Liu, Xingxing Huo","doi":"10.1093/jpp/rgae121","DOIUrl":"https://doi.org/10.1093/jpp/rgae121","url":null,"abstract":"<p><strong>Objectives: </strong>The study was aimed to investigate the effects of Xinfeng capsule (XFC) on tissue morphology, and gland function of the salivary gland (SG) in a primary Sjögren's syndrome (pSS) mouse model.</p><p><strong>Methods: </strong>An animal model of pSS was established by inducing SG protein in C57BL/6 mice. SG tissues were collected for tissue sequencing and subsequent experiments to detect the expression of cholinergic receptor muscarinic 3(M3R), early growth response factor 1 (EGR1) and target genes in the SG before and after XFC intervention, with in vitro validation.</p><p><strong>Results: </strong>Downstream targets of the EGR1 gene were predicted and analyzed using data analysis. EGR1 showed high expression and was selected for subsequent experiments. Administration of XFC significantly increased saliva production (P < 0.001) and reduced the extent of lymphatic infiltration observed in SG. Furthermore, the expression of EGR1 was increased in the model group with statistical significance in contrast with the control group but decreased after administration of XFC (P < 0.05). Data analysis predicted the downstream target of EGR1 as signal transducer and activator of transcription 3 (STAT3), which was validated in SG tissues of mice (P < .05).</p><p><strong>Conclusions: </strong>XFC demonstrated a significant improvement in the salivary secretion function of the SG in pSS mice. EGR1 can serve as a biomarker and therapeutic target for pSS.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468355","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}
Meiqi Wan, Anna Gan, Jun Dai, Fei Lin, Ruixuan Wang, Bo Wu, Tingxu Yan, Ying Jia
{"title":"Rhein induces apoptosis of AGS and MGC803 cells by regulating the Ras/PI3K/AKT and p38/MAPK signaling pathway.","authors":"Meiqi Wan, Anna Gan, Jun Dai, Fei Lin, Ruixuan Wang, Bo Wu, Tingxu Yan, Ying Jia","doi":"10.1093/jpp/rgae115","DOIUrl":"https://doi.org/10.1093/jpp/rgae115","url":null,"abstract":"<p><strong>Objectives: </strong>Rhein is one of the main bioactive compounds in the Polygonaceae plant, and has been proven to have anti-cancer activity in some reports. But the mechanism of Rhein in the treatment of gastric cancer (GC) is limited reported. In this research, network pharmacology combined with in vitro experiments was used for systematically studying the mechanism of Rhein.</p><p><strong>Methods: </strong>Network pharmacology confirmed the major effect signaling pathway and key targets of Rhein in the treatment of GC. Cell viability assay, colony formation assay, fluorescence probe assay, apoptosis assay, western blot and qRT-PCR verified the mechanism of Rhein in the treatment of GC cells (AGS and MGC803 cells).</p><p><strong>Key findings: </strong>The results showed that Rhein significantly induced the apoptosis process of AGS and MGC803 cells by regulating the Ras/phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and the p38/mitogen-activated protein kinase signaling pathways. The AKT activator (SC79) and p38 inhibitor (SB202190) inhibited Rhein-induced apoptosis.</p><p><strong>Conclusions: </strong>All results proved that Rhein could be recognized as a potential natural drug for the treatment of GC.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406534","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}
Faraha Ahmed, Syed Sufian Ahmad, Mohammad Mumtaz Alam, Mohammad Shaquiquzzaman, Mohammad Altamish, Anuja Krishnan, Divya Vohora, Abul Kalam Najmi, Mohammad Ahmed Khan
{"title":"Osteogenic effect of alogliptin in chemical-induced bone loss: a tri-modal in silico, in vitro, and in vivo analysis.","authors":"Faraha Ahmed, Syed Sufian Ahmad, Mohammad Mumtaz Alam, Mohammad Shaquiquzzaman, Mohammad Altamish, Anuja Krishnan, Divya Vohora, Abul Kalam Najmi, Mohammad Ahmed Khan","doi":"10.1093/jpp/rgae112","DOIUrl":"https://doi.org/10.1093/jpp/rgae112","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effects of Alogliptin in chemical-induced post-menopausal osteoporosis.</p><p><strong>Methodology: </strong>The binding affinity of alogliptin with osteogenic proteins was analysed in silico. The effect of alogliptin on osteogenic proteins and mineralization of osteoblastic cells was evaluated in UMR-106 cells. Further, in vivo anti-osteoporotic activity of alogliptin was evaluated in postmenopausal osteoporosis. Various bone turnover markers were assayed in serum. This followed the analysis of microarchitecture of bone, histology, and immunohistochemistry (IHC) of bone tissue.</p><p><strong>Results: </strong>Docking scores showed that alogliptin has binding affinity for bone alkaline phosphatase (BALP), osteocalcin, and bone morphogenic protein (BMP-2). Alogliptin also enhanced mineralization of osteoblast cells, evidenced with increased ALP, osteocalcin, and BMP-2. Animal studies revealed significant elevation of bone formation markers, bone ALP, osteocalcin and BMP-2, and decreased bone resorption markers, receptor activator of NF-κβ (RANKL), cathepsin K (CTSK), tartrate resistant acid phosphatase (TRAcP5b) in VCD-induced post-menopausal osteoporosis. Micro computed tomography (μCT) analysis and histology of femur bone and lumbar vertebrae demonstrated decrease in trabecular separation and improved bone density. IHC of femur showed reduced DPP4 enzyme.</p><p><strong>Conclusions: </strong>Alogliptin increased mineralization in osteoblast cells. It had beneficial effects also altered bone turnover markers, repaired the trabecular microstructure, improved bone mineral density, and exhibited bone forming capacity targeting DPP-4 enzyme in postmenopausal osteoporosis.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365642","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}
Benhur Judah Cury, Daniele Teixeira Jerônimo, Levy Mota da Silva, Thiago Farias de Queiroz E Silva, Tauani Caroline Santos França, Ana Caroline Dos Santos, Ian Richard Lucena Andriolo, José Roberto Santin, Larissa Benvenutti, Carlos Rafael Vaz, Mario Ferreira Conceição Santos, Jairo Bastos Kenupp, Luisa Mota da Silva
{"title":"Hydroalcoholic extract of Araucaria sp. brown propolis alleviates ulcerative colitis induced by TNBS in rats by reducing inflammatory cell infiltration and oxidative damage.","authors":"Benhur Judah Cury, Daniele Teixeira Jerônimo, Levy Mota da Silva, Thiago Farias de Queiroz E Silva, Tauani Caroline Santos França, Ana Caroline Dos Santos, Ian Richard Lucena Andriolo, José Roberto Santin, Larissa Benvenutti, Carlos Rafael Vaz, Mario Ferreira Conceição Santos, Jairo Bastos Kenupp, Luisa Mota da Silva","doi":"10.1093/jpp/rgae083","DOIUrl":"10.1093/jpp/rgae083","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effects of Araucaria sp. brown propolis (ABP) against trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats.</p><p><strong>Methods: </strong>Animals received vehicle (1% DMSO, 1 ml/kg) or hydroalcoholic extract of ABP (hydroalcoholic extract of Araucaria sp. brown propolis (HEABP), 30, 100, and 300 mg/kg) orally, or dexamethasone (25 mg/kg, s.c.) for 5 days. On day 4, the animals received intracolonic TNBS (150 mg/kg), on day 6 they were euthanized. The weight of the animals, the macroscopic and microscopic colonic damage, reduced glutathione (GSH) and malondialdehyde (MDA) levels, and the activity of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in colon homogenate. The action of HEABP and two isolated compounds in neutrophil migration was recorded.</p><p><strong>Key findings: </strong>HEABP (100 and 300 mg/kg), but not dexamethasone, decreased colonic lesion, and increased colonic mucin staining. In parallel, HEABP decreased MDA and restored GSH levels and the activity of SOD, CAT, and GST in the colon. A dose-dependent inhibition of MPO activity was observed (LogIC50 = 1.9). Moreover, HEBPA and the junicedric and abietic acids inhibited the neutrophil chemotaxis in vitro and HEBPA reduced neutrophil migration in vivo.</p><p><strong>Conclusion: </strong>HEABP may be promising in the therapies for inflammatory bowel diseases, reducing oxidative and inflammatory damage, especially mediated by neutrophils.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1379-1392"},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759412","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 the anxiolytic mechanism of Fructus gardeniae based on metabolomics, network pharmacology, and molecular docking.","authors":"Yue Tian, Fuli Yuan, Jiao Kong, Zhenshuang Yuan, Chunxue Jia, Hongqian Kui, Ziqiang Yin, Chuanxin Liu, Jianmei Huang","doi":"10.1093/jpp/rgad102","DOIUrl":"10.1093/jpp/rgad102","url":null,"abstract":"<p><strong>Objective: </strong>To explore the effect and anxiolytic mechanism of a natural remedy called Fructus gardeniae (FG).</p><p><strong>Methods: </strong>The elevated-plus maze (EPM) test was used to confirm the anxiolytic effect of FG. The potential and anxiolytic components, targets, and route processes of FG were investigated using the network pharmacology method in conjunction with metabolomics and molecular docking technologies.</p><p><strong>Results: </strong>FG could greatly enhance the proportion of time and times of opening arms, according to the EPM data. As to the metabolomics findings, a total of 61 distinct metabolites were found, mainly involved in glycine, serine, and threonine metabolism as well as alanine, aspartate, and glutamate metabolism. The primary active ingredients of FG, nicotiflorin, jasminodiol, and crocetin, demonstrated substantial binding affinities with monoamine oxidase A (MAOA), monoamine oxidase A (ACHE), malate dehydrogenase 2 (MDH2), glutamate decarboxylase 2 (GAD2), glutamate decarboxylase 1 (GAD1), and nitric oxide synthase (NOS1), according to the findings of network pharmacology and molecular docking.</p><p><strong>Conclusion: </strong>FG exerts an anxiolytic action via targeting MAOA, ACHE, MDH2, GAD2, GAD1, and NOS1, and regulating the metabolism of glycine, serine, and threonine as well as alanine, aspartic acid, and glutamic acid.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1310-1327"},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590596","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}
Melissa Kirkby, Akmal Hidayat Bin Sabri, Amy Holmes, Gary P J Moss, David Scurr
{"title":"PAMAM dendrimers as mediators of dermal and transdermal drug delivery: a review.","authors":"Melissa Kirkby, Akmal Hidayat Bin Sabri, Amy Holmes, Gary P J Moss, David Scurr","doi":"10.1093/jpp/rgae080","DOIUrl":"10.1093/jpp/rgae080","url":null,"abstract":"<p><strong>Objectives: </strong>Poly(amidoamine) dendrimers have been widely investigated as potential nanomaterials that can enhance the skin permeation of topically applied drugs. This article reviews the studies that have used dendrimers as penetration enhancers and examines the mechanisms by which enhancement is claimed.</p><p><strong>Key findings: </strong>A wide range of studies have demonstrated that, in certain circumstances and for certain drugs, the incorporation of dendrimers into a topically applied formulation can significantly increase the amount of drug passing into and through the skin. In some cases, dendrimers offered little or no enhancement of skin permeation, suggesting that the drug-dendrimer interaction and the selection of a specific dendrimer were central to ensuring optimal enhancement of skin permeation. Significant interactions between dendrimers and other formulation components were also reported in some cases.</p><p><strong>Summary: </strong>Dendrimers offer substantial potential for enhancing drug delivery into and across the skin, putatively by mechanisms that include occlusion and changes to surface tension. However, most of these studies are conducted in vitro and limited progress has been made beyond such laboratory studies, some of which are conducted using membranes of limited relevance to humans, such as rodent skin. Thus, the outcomes and claims of such studies should be treated with caution.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1284-1300"},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751974","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":"New insight into the molecular mechanism of TCM Bufei Huoxue formula for chronic obstructive pulmonary disease based on network pharmacology and experimental verification.","authors":"Yuanying Zhu, Shengyuan Hao, Yan Wu, Yuxian Lin, Xuecun Liu, Ting Luo, Yubing Zhou, Xin Yang, Hui Xu","doi":"10.1093/jpp/rgae071","DOIUrl":"10.1093/jpp/rgae071","url":null,"abstract":"<p><strong>Objectives: </strong>To unveil the mechanism of the Bufei Huoxue formula (BHF) for chronic obstructive pulmonary disease (COPD) through integrated network pharmacology (NP) and experimental verification.</p><p><strong>Methods: </strong>LC-MS was first applied to the analysis of both in vitro and in vivo samples from BHF for chemical profiling. Then a ligand library was prepared for NP to reveal the mechanism of BHF against COPD. Finally, verification was performed using an animal model related to the results from the NP.</p><p><strong>Key findings: </strong>A ligand library containing 170 compounds from BHF was obtained, while 357 targets related to COPD were filtered to construct a PPI network. GO and KEGG analysis demonstrated that bavachin, paeoniflorin, and demethylation of formononetin were the major compounds for BHF against COPD, which mainly by regulating the PI3K/Akt pathway. The experiments proved that BHF could alleviate lung injury and attenuate the release of TNF-α and IL-6 in the lung and BALF in a dose-dependent manner. Western blot further demonstrated the down-regulated effect of BHF on p-PI3K.</p><p><strong>Conclusion: </strong>BHF provides a potent alternative for the treatment of COPD, and the mechanism is probably associated with regulating the PI3K/AKT pathway to alleviate inflammatory injury by bavachin, paeoniflorin, and demethylation of formononetin.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1340-1351"},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036061","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":"Network pharmacology prediction, molecular docking, and molecular dynamics simulation-based strategy to explore the potential mechanism of Huashanshen dripping pill against asthma.","authors":"Xiaoyu Wang, Yansu Ji, Xin Jin, Miaomiao Zhou, Yujie Wu, Yanhong Xu, Rui Liu, Jihong Feng","doi":"10.1093/jpp/rgae081","DOIUrl":"10.1093/jpp/rgae081","url":null,"abstract":"<p><strong>Objectives: </strong>Asthma is a heterogeneous disease characterized by chronic airway inflammation. Huashanshen dripping pills (HSS) are commonly utilized for relieving asthma, relieving cough, and expelling phlegm. At present, the molecular mechanism against airway inflammation remains unclear.</p><p><strong>Methods: </strong>In this study, network pharmacology, molecular docking technology, and molecular dynamic simulation were used to predict the therapeutic pathways of HSS for asthma. The ovalbumin-induced mouse model was used to further validate the prediction by RT-qPCR, western blot, immunofluorescence, and related methods.</p><p><strong>Key findings: </strong>The findings indicate that HSS improves lung function and relieves lung inflammation by reducing inflammatory cell infiltration around the bronchus and reducing eosinophilic counts in bronchoalveolar lavage fluid (BALF). In addition, it lowers the levels of inflammatory cytokines and the expression levels of interleukin-4, interleukin-5, and interleukin-13 mRNA. HSS also inhibits the phosphorylation and nuclear translocation of NF-κB p65 protein.</p><p><strong>Conclusions: </strong>All results suggested that HSS can decrease airway inflammation in asthmatic mice by inhibiting NF-κB signaling pathway. This finding will shed light on how it can be used to treat asthma.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1362-1378"},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633786","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}
Meng Liang, Siyu Dong, Yi Guo, Yuyi Zhang, Xiao Xiao, Jun Ma, Xiaowen Jiang, Wenhui Yu
{"title":"Exploration of the potential mechanism of aqueous extract of Artemisia capillaris for the treatment of non-alcoholic fatty liver disease based on network pharmacology and experimental verification.","authors":"Meng Liang, Siyu Dong, Yi Guo, Yuyi Zhang, Xiao Xiao, Jun Ma, Xiaowen Jiang, Wenhui Yu","doi":"10.1093/jpp/rgae061","DOIUrl":"10.1093/jpp/rgae061","url":null,"abstract":"<p><strong>Objectives: </strong>Non-alcoholic fatty liver disease (NAFLD) is a nutritional and metabolic disease with a high prevalence today. Artemisia capillaris has anti-inflammatory, antioxidant, and other effects. However, the mechanism of A. capillaris in treating NAFLD is still poorly understood.</p><p><strong>Methods: </strong>This study explored the mechanism of A. capillaris in the treatment of NAFLD through network pharmacology and molecular docking, and verified the results through in vivo experiments using a high-fat diet-induced mouse model and in vitro experiments using an oleic acid-induced HepG2 cell model.</p><p><strong>Key findings: </strong>Aqueous extract of A. capillaris (AEAC) can reduce blood lipids, reduce liver lipid accumulation and liver inflammation in NAFLD mice, and improve NAFLD. Network pharmacology analysis revealed that 51 drug ingredients in A. capillaris correspond to 370 targets that act on NAFLD. GEO data mining obtained 93 liver differentially expressed genes related to NAFLD. In the UHPLC-MS detection results, 36 components were characterized and molecular docked with JNK. Verified in vitro and in vivo, the results show that JNK and the phosphorylation levels of IL-6, IL-1β, c-Jun, c-Fos, and CCL2 are key targets and pathways.</p><p><strong>Conclusions: </strong>This study confirmed that AEAC reduces lipid accumulation and inflammation in the liver of NAFLD mice by inhibiting the JNK/AP-1 pathway.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1328-1339"},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073130","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}