Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Exploring the bioactive ingredients of three traditional Chinese medicine formulas against age-related hearing loss through network pharmacology and experimental validation.","authors":"Wenying Shi, Qi Zhao, Hongwei Gao, Yaxin Yang, Zhiyong Tan, Na Li, Hongjie Wang, Yonghua Ji, You Zhou","doi":"10.1007/s00210-024-03464-2","DOIUrl":"10.1007/s00210-024-03464-2","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) formulas, including the Er-Long-Zuo-Ci pill, Tong-Qiao-Er-Long pill, and Er-Long pill, have long been utilized in China for managing age-related hearing loss (ARHL). However, the specific bioactive compounds, pharmacological targets, and underlying mechanisms remain elusive. This study aims to find the shared bioactive ingredients among these three formulas, uncover the molecular pathways they regulate, and identify potential therapeutic targets for ARHL. Furthermore, it seeks to validate the efficacy of these major components through both in vivo and in vitro experiments. Common bioactive ingredients were extracted from the TCMSP database, and their putative target proteins were predicted using the Swiss Target Prediction database. ARHL-related target proteins were collected from GeneCards and OMIM databases. Our approach involved constructing drug-target networks and drug-disease-specific protein-protein interaction networks and conducting clustering, topological property analyses, and functional annotation through GO and KEGG enrichment analysis. Molecular docking analysis was utilized to delineate interaction mechanisms between major bioactive ingredients and key target proteins. Finally, in vivo and in vitro experiments involving ABR recording, immunofluorescent staining, HE staining, and quantitative PCR were conducted to validate the treatment effects of flavonoids on the declining auditory function in DBA/2 J mice. We identified 11 common chemical compounds across the three formulas and their associated 276 putative targets. Additionally, 3350 ARHL-related targets were compiled. As an intersection of the putative targets of the common compounds and ARHL-related proteins, 145 shared targets were determined. Functional enrichment analysis indicated that these compounds may modulate various biological processes, including cell proliferation, apoptosis, inflammatory response, and synaptic connections. Notably, potential targets such as TNFα, MAPK1, SRC, AKT, EGFR, ESR1, and AR were implicated. Flavonoids emerged as major bioactive components against ARHL based on target numbers, with molecular docking demonstrating diverse interaction models between these flavonoids and protein targets. Furthermore, baicalin could mitigate the age-related cochlear damage and hearing loss of DBA/2 J mice through its multi-target and multi-pathway mechanism, involving anti-inflammation, modulation of sex hormone-related pathways, and activation of potassium channels. This study offers an integrated network pharmacology approach, validated by in vivo and in vitro experiments, shedding light on the potential mechanisms, major active components, and therapeutic targets of TCM formulas for treating ARHL.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3731-3759"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361803","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":"Fluoxetine promotes the recovery of dysphagia and improves nutritional status and neurotrophic status in dysphagia patients after acute ischemic stroke.","authors":"Yi Su, Youguo Hao, Xianjing Zeng, Jing Li","doi":"10.1007/s00210-024-03465-1","DOIUrl":"10.1007/s00210-024-03465-1","url":null,"abstract":"<p><p>This study aimed to investigate the effects of fluoxetine on swallowing function, neurotrophic factors, and psychological status in patients with dysphagia after acute ischemic stroke (AIS). A total of 118 patients with dysphagia after AIS who were diagnosed and treated in our hospital from July 2020 to March 2022 were selected as the study objects with 59 cases in each group. Patients in the control group underwent routine treatment and swallowing rehabilitation without fluoxetine. Patients in the study group received routine treatment, swallowing rehabilitation, and fluoxetine treatment. The quality of life was compared according to the Generic Quality of Life Inventory-74 (CQOLI-74). Patients were followed for 90 days, and the grades were compared with the Modified Rankin Scale (mRS). The total effective rate of the study group was 84.75%, which was higher than that of the control group with 62.71% (χ² = 7.394, P < 0.05). The life quality scores of the two groups were both dramatically elevated compared to those before the treatment, and the study group had a sensibly higher life quality score than the control group (P < 0.05). The proportion of grade 4~5 in the study group was significantly lower than that in the control group (χ² = 492, P < 0.05). The total incidence of adverse reactions in the control group was 5.08% (3/59), which was significantly lower than that in the study group with 11.86% (7/59) (χ² = 1.748, P = 0.186). Fluoxetine has a significant effect on the treatment of dysphagia after AIS by enhancing the recovery of dysphagia and promoting the recovery of neurological function.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3761-3773"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361804","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":"Sex differences in the orofacial antinociceptive effect of metformin and the role of transient receptor potential channels.","authors":"Sacha Aubrey Alves Rodrigues Santos, Marina de Barros Mamede Vidal Damasceno, Barry John Sessle, Antônio Eufrásio Vieira-Neto, Gerlânia de Oliveira Leite, Francisco Ernani Alves Magalhães, Kaio César Simiano Tavares, Samara Casemiro Benevides, Adriana Rolim Campos","doi":"10.1007/s00210-024-03475-z","DOIUrl":"10.1007/s00210-024-03475-z","url":null,"abstract":"<p><p>Metformin is classified as a biguanide and is used in the treatment of type 2 diabetes. It is used worldwide and has been investigated in drug repositioning. The present study aims to investigate whether there is sexual dimorphism in the orofacial antinociceptive effect of metformin and the participation of TRP channels. Acute nociceptive behavior was induced by administering cinnamaldehyde or capsaicin to the upper lip. Nociceptive behavior was assessed through orofacial rubbing, and the effects of pre-treatment with metformin (125 or 250 mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The chronic pain model involved infraorbital nerve transection (IONX) was evaluated using Von Frey electronic filaments. Trpv1 gene expression was analyzed in the nerve ganglion. Docking experiments were performed. Metformin, but not the vehicle, produced antinociception (p < 0.0001) in all acute nociceptive behaviors in both sexes, and these effects were attenuated by the TRPV1 antagonist capsazepine and the TRPA1 antagonist HC-030031. In IONX with better (**p < 0.01, ****p < 0.0001 vs. control) results in females. TRPV1 gene expression was observed in the metformin treated group (*p < 0.05 vs. control). Docking experiments revealed that metformin may interact with TRPV1 and TRPA1 channels. Metformin promotes orofacial antinociception in both sexes in acute pain and is more effective in chronic pain in females than in males, through the modulation of TRPV1 and TRPA1 channels. These preclinical findings suggest a potential repositioning of metformin as an analgesic agent in acute and chronic orofacial pain states.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3775-3788"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361806","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":"VSIG-3/IGSF11 silencing in A2058 melanoma cells simultaneously suppresses melanoma progression and induces anti-tumoral cytokine profile in human T cells: In silico and in vitro study.","authors":"Najibeh Shekari, Dariush Shanehbandi, Elham Baghbani, Sahar Safaei, Javad Masoumi, Behzad Baradaran, Seyed Amir Jalali","doi":"10.1007/s00210-024-03491-z","DOIUrl":"10.1007/s00210-024-03491-z","url":null,"abstract":"<p><p>VISTA is a newly discovered immune checkpoint whose functional mechanisms have become increasingly important to study due to its brilliant results in cancer immunotherapy. Despite VSIG-3/IGSF11 being identified as an inhibitory ligand for VISTA with potential as a target for cancer immunotherapy, very little is known of its functions. This study aimed to conduct a detailed analysis of VSIG-3/IGSF11 in melanoma, as well as to study the effects of its silencing on melanoma cell line progression and human T cell functions. Online databases were used to investigate VSIG-3/IGSF11 expression, its relationships, and prognostic value in melanoma. Then, the effects of VSIG-3/IGSF11 silencing on proliferation, migration, cell cycle arrest, and apoptosis in A2058 melanoma cells were assessed using MTT, colony formation, wound healing, cell cycle, and Annexin-V FITC/PI assays, respectively. Finally, A2058 cells transfected with VSIG-3/IGSF11 siRNA were co-cultured with human T cells, and the expression levels of T cell cytokines were evaluated using qRT-PCR. VSIG-3/IGSF11 expression was significantly increased in melanoma patients and cell lines; however, no correlation was found between VSIG-3/IGSF11 expression levels and clinicopathological characteristics, survival, or immune cell infiltration. Following VSIG-3/IGSF11 silencing in A2058 cells, viability, proliferation, and migration rates were decreased, while apoptosis was increased. T cells co-cultured with VSIG-3/IGSF11 siRNA-transfected A2058 cells exhibited increased expression levels of IFN-γ and IL-12 and decreased expression levels of IL-10, TGF-β, and TNF-α. The inhibitory effect of VSIG-3/IGSF11 silencing on A2058 melanoma cell progression, along with the alteration of T cell cytokines towards a pro-inflammatory phenotype, suggests that VSIG-3/IGSF11 is primarily involved in melanoma progression and modulating immune responses. Therefore, it may be a valuable target for immunotherapy in melanoma patients.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3861-3880"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372349","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":"Protective effect of aspirin and gentisic acid, a plant-derived phenolic acid, on acrylamide-induced neurotoxicity by inhibiting apoptosis and autophagy.","authors":"Yasaman Hosseinzadeh, Mahboobeh Ghasemzadeh Rahbardar, Soghra Mehri, Bibi Marjan Razavi, Hossein Hosseinzadeh","doi":"10.1007/s00210-024-03498-6","DOIUrl":"10.1007/s00210-024-03498-6","url":null,"abstract":"<p><p>Acrylamide (ACR) is a toxic agent for humans and animals. Gentisic acid, an aspirin metabolite, has antioxidant activity. Therefore, the present study investigated the probable protective effects of aspirin and gentisic acid on ACR-induced neurotoxicity in PC12 cells and rats. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the effects of aspirin and gentisic acid (1.25, 2.5, 5 µM) on ACR (5 mM) toxicity. Male Wistar rats were randomly divided into 13 groups: (1) Control group, (2) ACR (50 mg/kg, 11 days, i.p.), (3-5) ACR + aspirin (25, 50, 75 mg/kg, 11 days, p.o.), (6-8) ACR + gentisic acid (25, 50, 75 mg/kg, 11 days, p.o.), (9) ACR + vitamin E (200 mg/kg, every other day, i.p.), (10, 11) Aspirin (75, 100 mg/kg, 11 days, p.o.), (12, 13) Gentisic acid (75, 100 mg/kg, 11 days, p.o.). Behavioral tests were assessed on the final day of the study. In the cerebral cortex, malondialdehyde (MDA), glutathione (GSH), cleaved-caspase-3, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein levels were evaluated. When compared with the ACR group, aspirin (2.5, 5 µM) and gentisic acid (2.5 µM) significantly enhanced cell viability. In comparison to the control group, ACR induced severe motor impairment, elevated MDA, cleaved-caspase-3, LC3 II/I ratio, and decreased GSH levels in the cerebral cortex of rats. ACR-induced changes were significantly reversed by aspirin and gentisic acid (25 mg/kg). Oxidative stress, apoptosis, and autophagy play important roles in the neurotoxicity of ACR. Aspirin and gentisic acid significantly reduced ACR-induced toxicity by inhibiting the mentioned mechanisms.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3895-3911"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378110","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":"Long-term enzyme replacement therapy in Fabry patients protects against oxidative and inflammatory process.","authors":"Alana Pimentel Moura, Tatiane Grazieli Hammerschmidt, Gilian Guerreiro, Camila Aguilar, Jéssica Lamberty Faverzani, Franciele Fátima Lopes, Fabiano de Oliveira Poswar, Roberto Giugliani, Marion Deon, Carmen Regla Vargas","doi":"10.1007/s00210-024-03499-5","DOIUrl":"10.1007/s00210-024-03499-5","url":null,"abstract":"<p><p>Fabry disease (FD) is an X-linked recessive lysosomal storage disorder, characterized by a deficiency of α-galactosidase, which causes the progressive accumulation of glycosphingolipids, especially globotriaosylsphingosine (Gb3), in lysosomes across multiple organs. Substrate deposition, associated with tissue damage in FD, also contributes to the emergence of a pro-inflammatory state presented by some patients. We investigated pro- and anti-inflammatory cytokines, and the expression of inflammation-associated genes in treated FD patients, as well as oxidative parameters. We found a decrease in the production of cytokines IL-1β, IL-6, IL-10, and TNF-α in male FD patients and a normalization of redox status in male and female FD patients, once the levels of protein, lipid oxidation, and nitrite and nitrate content were like healthy individuals. Our results suggest that long-term ERT in men with FD contributes to the reduction of a pro-inflammatory scenario and a decrease of oxidative damage in patients, reflecting greater control throughout the disease and in the multisystemic changes characteristic of this disorder. These findings lead us to believe that long-term ERT can improve the redox status and protect these individuals against oxidative and nitrative stress, as well as the inflammatory process.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4211-4218"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470329","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":"Chronic stress-mediated dysregulations in inflammatory, immune and oxidative circuitry impairs the therapeutic response of methotrexate in experimental autoimmune disease models.","authors":"Rishabh Chaudhary, Mohd Akhtar Azam, Bhavana Dowand, Alpana Singh, Mujeeba Rehman, Vipul Agarwal, Anand Kumar, Arjun Singh Kaushik, Sukriti Srivastava, Siddhi Srivastava, Vikas Mishra","doi":"10.1007/s00210-024-03529-2","DOIUrl":"10.1007/s00210-024-03529-2","url":null,"abstract":"<p><p>Chronic stress is significantly implicated in the worsening of autoimmune disorders, contributing to elevated inflammation and diminished therapeutic efficacy. Here, in this study, we investigated the detrimental impact of an 8-week chronic unpredictable stress (CUS) protocol on the progression of arthritis and psoriasis using collagen-induced arthritis (CIA) and imiquimod (IMQ)-induced psoriasis rat models, respectively. Our objective was to elucidate how prolonged stress exacerbates disease severity and impairs the effectiveness of treatment drug. Following the induction of CIA and IMQ, rats were subjected to an 8-week CUS paradigm designed to simulate chronic stress conditions. Moreover, after 5 weeks of CUS, methotrexate (MTX; 2 mg/kg, administered once weekly for 3 weeks, intraperitoneally) was introduced as a therapeutic intervention. The severity of CUS-induced effects and the therapeutic impairment of MTX in arthritis and psoriasis rats were assessed through pathological examination of joint and epidermal tissues, respectively. Additionally, we measured various pro-inflammatory cytokine levels, including NF-κB (nuclear factor kappa B), IFN-γ (interferon-gamma), TNF-α (tumour necrosis factor alpha), IL (interleukin)-1β, IL-6, IL-17 and IL-23 using enzyme-linked immunosorbent assay (ELISA), analysed immune cells through complete haematological profiling and evaluated oxidative stress markers. Our findings revealed that CUS significantly aggravated the pathological features of both arthritis and psoriasis. Prolonged stress exposure led to heightened inflammatory responses, increased oxidative stress and more severe tissue damage. Moreover, the therapeutic efficacy of MTX was notably reduced in stressed rats compared to non-stressed, underscoring the detrimental effects of chronic stress on treatment outcomes. Taken together, our results emphasize the importance of considering chronic stress as a critical factor in the management of autoimmune diseases.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4305-4334"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504427","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":"Development of bacterial resistance in Germany from 2008 to 2022 - major culprit pathogens, antibacterial drugs, and prescribing practices.","authors":"Lilly Josephine Bindel, Roland Seifert","doi":"10.1007/s00210-024-03533-6","DOIUrl":"10.1007/s00210-024-03533-6","url":null,"abstract":"<p><p>Rising bacterial resistance is a global threat, causing rising financial burdens on healthcare systems and endangering effective treatment of bacterial infections. To ensure the efficacy of antibacterial drugs, it is essential to identify the most dangerous pathogens and vulnerable antibacterial drugs. Previous research by our group suggested irrational outpatient prescribing practices in Germany, supporting a growing bacterial resistance. This study analyses developments and characteristics for the ten most prescribed antibacterial drugs in Germany from 2008 to 2022. Conclusions are based on the development of bacterial resistance levels and an analysis of correlations between pathogens. We identified cefuroxime axetil, sulfamethoxazole-trimethoprim and nitrofurantoin as the most problematic drugs. Particularly problematic pathogens include E. faecalis, E. faecium, K. pneumoniae, and P. mirabilis. Besides increasing bacterial resistance, they are characterised by a high proportion of significant positive correlations, indicating a high potential for mutually reinforcing resistance development. Alarmingly, most of the antibacterial drugs analysed showed a growing resistance to at least one of the analysed pathogens. In most cases, the best treatment option is threatened by increasing bacterial resistance. We also identified several differences between current bacterial resistance data and therapeutic guidelines. In aggregate, our findings support irrational prescribing behaviour and underscore the urgent need for improved prescribing practices to counter rising bacterial resistance in Germany. Moreover, therapeutic guidelines for bacterial infections, the \"holy grail\" of pharmacotherapy, must be updated more frequently.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4219-4236"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504428","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":"TRIM7 knockdown protects against LPS-induced autophagy, ferroptosis, and inflammatory responses in human bronchial epithelial cells.","authors":"Qian Li, Ling Gao","doi":"10.1007/s00210-024-03546-1","DOIUrl":"10.1007/s00210-024-03546-1","url":null,"abstract":"<p><p>Asthma is one of the most common respiratory diseases in pediatric department. Several asthma-associated events including inflammatory responses, autophagy, and ferroptosis have been identified as typical pathological processes. TRIM7 is a member of TRIM proteins family associated with several types of diseases. Nevertheless, its role in asthma is still elusive. The current research showed that TRIM7 was involved in the pathogenesis of asthma mainly by regulating the Akt signaling pathway. In detail, we found that TRIM7 was highly expressed in patients with asthma and in an in vitro model of asthma. The following analysis indicated that TRIM7 knockdown attenuated the expression and secretion of inflammatory cytokines including TNF-α, IL-1β and IL-6 in lipopolysaccharide (LPS)-exposed human bronchial epithelial cells (HBECs). Meanwhile, knockdown of TRIM7 exerted inhibitory effects on LPS-induced autophagy and ferroptosis. Further mechanistic studies showed that TRIM7 knockdown inhibited LPS-induced activation of Akt pathway, while overexpression of Akt attenuated the inhibitory effects of TRIM7 knockdown on LPS-exposed HBECs. Collectively, we reported here that TRIM7 knockdown inhibited LPS-induced autophagy, ferroptosis, and inflammatory cytokine secretion in HBECs via regulating the Akt pathway, providing a new insight into the strategies for improving asthma treatments.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4265-4277"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504435","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":"Carvacrol potentiates immunity and sorafenib anti-cancer efficacy by targeting HIF-1α/STAT3/ FGL1 pathway: in silico and in vivo study.","authors":"Eman H Yousef, Amal M El Gayar, Nada F Abo El-Magd","doi":"10.1007/s00210-024-03530-9","DOIUrl":"10.1007/s00210-024-03530-9","url":null,"abstract":"<p><p>Hypoxia and tumor cell immunological escape greatly hinder the hepatocellular carcinoma (HCC) treatment efficiency. This study is designed to investigate the capability of carvacrol (CVR) to enhance sorafenib (SOR) anti-cancer efficacy and modulate anti-HCC immunity. CVR target and biological activities were predicted using Swiss Target Prediction website and PASS web server. UALCAN and LinkedOmics databases were used to examine hypoxia-inducible factor 1-alpha (HIF-1α) expression and the relationship between studied genes and tumor clinical features. Kaplan-Meier plotter (KM plotter) and TISIDB databases were used to illustrate correlation of HIF-1α with HCC prognosis and immune infiltration. The binding affinities of CVR to p300, KAT2B, CREBBP, and Hsp90 were demonstrated by molecular docking. In vivo analysis was performed in male Sprague-Dawley rats. The STAT3, JAK2, and fibrinogen-like protein 1 (FGL1) expressions were assessed by qRT-PCR. FGL1 was determined by ELISA. CD8⁺ T cell number was counted by flow cytometry. HIF-1α was determined by immunohistochemistry. CVR showed an HIF-1α inhibitory potential, which is highly expressed in HCC tissues. Also, elevated HIF-1α expression has been found to be correlated with clinicopathological characteristics, poor survival in HCC patients, and tumor immune cell infiltration. CVR/SOR enhanced liver functions and decreased AFP level. CVR/SOR hindered HCC progression by downregulating STAT3, JAK2, and FGL1. CVR/SOR induced tumor immunity via increasing CD8⁺ T cells. CVR/SOR is a powerful combination for tumor repression and enhancing SOR efficiency in HCC by modulating FGL1. Moreover, CVR/SOR might exert the aforementioned effects through HIF-1α/STAT3/FGL1 pathway.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4335-4353"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522485","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}