Current molecular pharmacology最新文献

{"title":"The Role of Complement Component 3 (C3) in Psoriasis.","authors":"Qiong Cao, Junqin Li, Kaiming Zhang","doi":"10.2174/0118761429361884250318071733","DOIUrl":"10.2174/0118761429361884250318071733","url":null,"abstract":"<p><p>Psoriasis is a chronic inflammatory disease driven by immune dysfunction, with its pathogenesis still not fully understood. This article explores the crucial roles of complement molecules in psoriasis, emphasizing complement C3's pathogenic mechanisms and its potential as a therapeutic target. The complement system's structure and function highlight its significance in immune response and inflammation regulation. This system is activated through the classical, alternative, and lectin pathways, with complement C3, primarily produced by hepatocytes and macrophages, serving as a core component and the most abundant complement in serum. The article analyzes C3's structure and biological functions to reveal its pathogenic roles in psoriasis, detailing its specific mechanisms in immune abnormalities and skin lesions as supported by recent studies. The activation of the complement system leads to C3 convertase formation, cleaving C3 into C3a and C3b. T cells, though expressing lower C3 levels, produce C3a and C3b, regulating vital T cell functions like CD4+ T cell differentiation and survival. The review also summarizes current therapeutic strategies targeting C3, evaluating their potential effectiveness in alleviating psoriasis symptoms. C3aR inhibitors, such as SB290157, can slow disease progression, proposing a novel therapeutic approach for psoriasis. This comprehensive review offers new insights and theoretical foundations for complement C3 as a target for psoriasis treatment, aiming to advance future research and clinical interventions.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429361884"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of miRNAs in Podocyte Injury in Diabetic Nephropathy: Mechanisms and Clinical Applications.","authors":"Shan Hu, Jiafu Yan, Qiong Yuan, Tianjiao Meng, Zhi Cai, Yuanshuai Huang, Yuhan Wang","doi":"10.2174/0118761429363169250313083148","DOIUrl":"10.2174/0118761429363169250313083148","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is one of the most frequent complications of diabetes and, if left uncontrolled, can progress to renal failure. In the early stage of DKD, significant pathological changes occur in podocytes, leading to proteinuria. However, the mechanism of pathological changes in podocytes has not been clarified. Existing clinical diagnostic methods tend to overlook these subtle pathophysiological changes in the early stages, leading to missed optimal treatment time. Moreover, existing treatment methods are limited. Emerging evidence strongly suggests that podocyte injury is associated with distinct specific miRNA expression profiles that precede the onset of overt proteinuria and glomerular filtration rate decline. This review explores the role of microRNAs in podocyte damage-related pathways in DKD, such as reactive oxygen species (ROS) production and inflammatory responses. Furthermore, we discuss the potential clinical application of miRNAs as molecular markers and their feasibility as a molecular therapy.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429363169"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Roles of mTOR Signaling in Nasopharyngeal Carcinoma: From Pathogenesis to Therapy","authors":"Ting Gong, Gui Cao, Danyang Sun, Tongtong Ge, Ping Li","doi":"10.2174/0118761429293675240709061332","DOIUrl":"10.2174/0118761429293675240709061332","url":null,"abstract":"<p><p>Nasopharyngeal carcinoma (NPC) is an epithelial malignancy caused by cancer of the mucosal epithelial cells of the nasopharynx. Most patients with NPC present with distant metastases and treatment resistance, both of which challenge current anti-tumour drugs. The mammalian target of the rapamycin (mTOR) signalling pathway is one of the most highly activated signalling pathways in NPC and plays an important role in various cellular activities. Dysfunction of mTOR and related signalling pathways induces tumour metabolism and growth. In this review, we summarize current evidence to evaluate the potential mechanisms by which mTOR is implicated in NPC. It was found that activating mTOR and its upstream and downstream signalling can promote tumor growth and survival of NPC. It is possible that EMT and autophagy regulated by cellular mTOR signalling activities may be implicated in the metastases and radioresistance of NPC.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429293675"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Chrysin and Chrysin Nanocrystals on Chlorpyrifos-Induced Dysfunction of the Hypothalamic-Pituitary-Testicular Axis in Rats","authors":"Tahereh Farkhondeh, Babak Roshanravan, Fariborz Samini, Saeed Samarghandian","doi":"10.2174/0118761429305457240826093330","DOIUrl":"10.2174/0118761429305457240826093330","url":null,"abstract":"<p><strong>Aims and background: </strong>The escalating global concerns regarding reproductive health underscore the urgency of investigating the impact of environmental pollutants on fertility. This study aims to focus on Chlorpyrifos (CPF), a widely-used organophosphate insecticide, and explores its adverse influence on the hypothalamic-pituitary-testicular axis in Wistar male rats. This study explores the potential protective effects of chrysin nanocrystal (CHN), a flavonoid with known antioxidant and anti-inflammatory properties, against CPF-induced impairments in male Wistar rats.</p><p><strong>Methods: </strong>Chrysin nanocrystals were prepared using a solvent precipitation method. Six sets of male Wistar rats were subjected to 30 days of treatment, comprising a control group, a group treated solely with CPF, groups treated with CHN at doses of 5 mg/kg and 10 mg/kg, and groups co-treated with CPF and CHN. Serum levels of reproductive hormones, enzyme biomarkers of testicular function, oxidative stress, and inflammatory biomarkers were assessed. Additionally, histological examinations were conducted on the hypothalamus, testes, and epididymis.</p><p><strong>Results: </strong>CHN exhibited antioxidant and anti-inflammatory properties, effectively counteracting CPF-induced reductions in Luteinizing Hormone (LH), serum testosterone, Follicle-Stimulating Hormone (FSH), and testicular enzyme biomarkers. Moreover, CHN enhanced antioxidant defenses, as evidenced by decreased malondialdehyde (MDA) and increased glutathione (GSH) levels in the hypothalamus, and testes, epididymis. Inflammatory markers, including nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were significantly reduced in CHN co-treated groups compared to the CPF-only group. Histopathological analyses confirmed the protective effects of CHN on tissue integrity.</p><p><strong>Conclusion: </strong>Chrysin nanocrystal demonstrated promising potential in mitigating CPF-induced reproductive deficits in male rats through its anti-inflammatory and antioxidant properties. This study provides valuable insights into therapeutic interventions against environmental toxin-induced reproductive toxicity, emphasizing the potential of chrysin nanocrystals as a protective agent in the context of CPF exposure.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429305457"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fenofibrate Inhibits LPS and Zymosan-induced Inflammatory Responses through Sonic Hedgehog in IMG Cells.","authors":"Yu-Wen Wang, Bor-Ren Huang, Dah-Yuu Lu, Jin-Wun Chen, Vichuda Charoensaensuk, Liang-Yo Yang, Sheng-Wei Lai, Cheng-Fang Tsai, Wei-Lan Yeh","doi":"10.2174/0118761429317532241017051135","DOIUrl":"10.2174/0118761429317532241017051135","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammatory responses are strongly associated with the pathogenesis of progressive neurodegenerative conditions and mood disorders. Modulating microglial activation is a potential strategy for developing protective treatments for central nervous system (CNS)-related diseases. Fibrates, widely used in clinical practice as cholesterol-lowering medications, exhibit numerous biological activities, such as anticancer and antiinflammatory activities. However, the mechanisms underlying their beneficial effects on the CNS remain unclear.</p><p><strong>Objective: </strong>This study investigated the mechanisms through which fibrates influence inflammatory and anti-inflammatory homeostasis in microglial cells.</p><p><strong>Methods: </strong>Cell viability assay, nitric oxide measurement, Western blot analysis,, real-time PCR, and cell transfection were used in this study.</p><p><strong>Results: </strong>Fenofibrate, a well-known fibrate, reduced the production of nitric oxide and interleukin-6 and the expression of inducible nitric oxide synthase and cyclooxygenase-2 in microglial cells. It also inhibited the expression of various proinflammatory cytokines and chemokines, including tumor necrosis factor-ɑ and interleukin-1&#946;, and chemokine (C-C) motif ligand 2 and chemokine (C-X-C motif) ligand 10. Notably, treatment of fenofibrate dramatically activated the sonic hedgehog (SHH) and sirtuin-1 (SIRT1). Furthermore, the inhibition of SHH or SIRT1 mitigated the anti-inflammatory effects of fenofibrate in IMG microglial cells.</p><p><strong>Conclusion: </strong>Our findings suggest that fenofibrate may inhibit inflammatory responses by activating SIRT1 and SHH in IMG microglial cells. Our study suggests that fenofibrate or targeting SHH molecule is a promising therapeutic strategy for neuroinflammation-associated conditions. Further research with additional cell lines and in vivo models is needed to understand its therapeutic potential.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 1","pages":"e18761429317532"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutations in Rv0678, Rv2535c, and Rv1979c Confer Resistance to Bedaquiline in Clinical Isolates of Mycobacterium Tuberculosis.","authors":"Khaoula Balgouthi, Manaf AlMatar, Hamza Saghrouchni, Osman Albarri, Işıl Var","doi":"10.2174/0118761429314641240815080447","DOIUrl":"10.2174/0118761429314641240815080447","url":null,"abstract":"<p><strong>Introduction: </strong>Reduced bedaquiline (BDQ) sensitivity to antimycobacterial drugs has been linked to mutations in the Rv0678, pepQ, and Rv1979c genes of Mycobacterium tuberculosis (MTB). Resistance-causing mutations in MTB strains under treatment may have an impact on novel BDQ-based medication regimens intended to reduce treatment time. Due to this, we investigated the genetic basis of BDQ resistance in Turkish TB patients with MTB clinical isolates. Furthermore, mutations in the genes linked to efflux pumps were examined as a backup resistance mechanism.</p><p><strong>Methods: </strong>We scrutinized 100 MTB clinical isolates from TB patients using convenience sampling. Eighty MDR and twenty pan-drug susceptible MTB strains were among these isolates. Sequencing was performed on all strains, and genomic analyses were performed to find mutations in BDQ resistance-associated genes, including Rv0678 and pepQ(Rv2535c), which correspond to a putative Xaa-Pro aminopeptidase, and Rv1979c. Of the 74 isolates with PepQ (Rv2535c) mutations, four isolates (2.96%) exhibited MGIT-BDQ susceptibility.</p><p><strong>Results: </strong>Twenty-one (19.11%) of the ninety-one isolates carrying mutations, including Rv1979c, were MGIT-BDQ-sensitive. Nonetheless, out of the 39 isolates with Rv0678 mutations, four (2.96%) were sensitive to MGIT-BDQ. It was found that resistance-associated variants (RAVs) in Rv0678, pepQ, and Rv1979c are often linked to BDQ resistance.</p><p><strong>Conclusion: </strong>In order to include variations in efflux pump genes in genome-based diagnostics for drug-resistant MTB, further evidence about their involvement in resistance is needed.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429314641"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Airway Remodeling in Asthma: Anti-EMT Effects of Xuanfei Pingchuan Prescription <i>via</i> TGFβ1/Smad Pathway Modulation.","authors":"Lu Zou, Xiao Yu, Ling Tang, Chunrong Guo, Zhumei Sun, Shaobin Li, Yanqi Cheng, Fufeng Li, Hong Fang","doi":"10.2174/0118761429360075250320062131","DOIUrl":"10.2174/0118761429360075250320062131","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a chronic airway disease characterized by Airway Remodeling (AR) and persistent inflammation, with Epithelial-Mesenchymal Transition (EMT) playing a crucial role in fibrosis and smooth muscle proliferation. The Transforming Growth Factor-Beta1 (TGFβ1)/Smad pathway is a key driver of EMT in asthma. Current treatments do not effectively prevent AR progression. Traditional Chinese Medicine, particularly the Xuanfei Pingchuan (XFPC) prescription, has shown potential in managing asthma, but its role in EMT regulation remains unclear.</p><p><strong>Methods: </strong>This study explored the role of \"phlegm and stasis\" in airway remodeling (AR) in asthma from the perspective of EMT and investigated the effects and underlying mechanisms of XFPC prescription on EMT in AR. <i>In vitro</i>, human bronchial epithelial (16HBE) cells were induced into EMT with TGFβ1 and treated with XFPC drug-containing serum, with EMT marker expression analyzed <i>via</i> RT-qPCR and Western blot. <i>In vivo</i>, an ovalbumin (OVA)-induced asthma model in Sprague Dawley rats was used to evaluate the effects of different XFPC doses through histopathology, immunofluorescence, and molecular analyses. Additionally, Smurf2 cDNA transfection was conducted to assess the role of Smurf2 in EMT regulation.</p><p><strong>Results: </strong>The results confirmed that XFPC prescription suppressed the pathway of transforming-growth factor-beta1 (TGFβ1)-Smad by reducing Smad ubiquitination regulator 2 (Smurf2), Smad2, Smad3, TGFβ1 receptor (TβRI), N-cadherin, α-SMA, and Vimentin in terms of expressions at messenger ribonucleic acid (mRNA) and protein levels. However, XFPC prescription up-regulated expressions of SnoN and E-cadherin at protein and mRNA levels to inhibit EMT. The result also confirmed that XFPC prescription decreased the ubiquitination of Smad7.</p><p><strong>Conclusion: </strong>XFPC prescription could suppress AR in TGFβ1 induced 16HBE cells and OVA-sensitized animal models through TGFβ1/Smad pathway.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 ","pages":"e18761429360075"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Local Angiotensin II/Angiotensin Type 1 Receptor in Endometriosis: A Potential Target for New Treatment Approaches","authors":"Shirin Moazen, Mohammad-Hassan Arjmand","doi":"10.2174/0118761429315431240712100124","DOIUrl":"10.2174/0118761429315431240712100124","url":null,"abstract":"<p><p>Endometriosis is a chronic inflammatory disorder described by the presence of functional endometrial-like tissues at extra-uterine locations that are related to chronic pelvic pain and infertility. Multiple molecular mechanisms, including inflammation, reactive oxygen species (ROS) generation, fibrotic reactions, and angiogenesis, are involved in the pathogenesis of endometriosis; however, the exact cause of this disorder still remains a matter of discussion. Recently, it has been shown that the local renin-angiotensin system (RAS) has been expressed in different tissues, like the gynecological tract, and alterations in its expression are associated with multiple pathological conditions like endometriosis. Angiotensin II (Ang II), as a main peptide of the RAS through angiotensin type 1 receptor (AT1R), upregulates signal transduction pathways such as nuclear factor kappa B (NF-κB), mitogen activation protein kinase (MAPK), and transforming growth factor beta (TGF-β) to promote inflammation, oxidative stress, and fibrogenesis. Angiotensin receptor blockers (ARBs) control high blood pressure, which is increased by excessive AT1R activity. Recently, it has been recognized that ARBs have tissue protective effects because of their anti-inflammatory and antifibrotic effects. In this review, we focused on the role of local Ang II/AT1R axis activity in endometriosis pathogenesis and justified the use of ARB agents as a potential therapeutic strategy to improve endometriosis.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429315431"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of LncRNA WT1-AS Inhibits Tumor Growth and Promotes Autophagy in Gastric Cancer via Suppression of PI3K/Akt/mTOR Pathway.","authors":"Xiaobei Zhang, Meng Jin, Xiaoying Yao, Jilan Liu, Yonghong Yang, Jian Huang, Guiyuan Jin, Shiqi Liu, Baogui Zhang","doi":"10.2174/0118761429318398240918063450","DOIUrl":"10.2174/0118761429318398240918063450","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence has highlighted the involvement of the imbalance of long non-coding RNAs in the development of gastric cancer (GC), which is one of the most common malignancies in the world. This study aimed to determine the role of lncRNA WT1-AS in the progression of GC and explore its underlying mechanism.</p><p><strong>Methods: </strong>The expression of lncRNA WT1-AS in gastric cancer tissues was detected using RT-qPCR. We knocked down the expression of WT1-AS in GC cells or treated them with rapamycin or both. Then, transwell assay and scratch assay were carried out to determine the migration of GC cells, and flow cytometry was carried out to determine the cell cycle. The immunofluorescence technique was used to determine the autophagy, and a tumor formation experiment was carried out to determine tumor growth <i>in vivo</i>. The expression of factors related to the PI3K/Akt/mTOR pathway was also measured by Western Blotting.</p><p><strong>Results: </strong>In GC tissues and cells, lncRNA WT1-AS was underexpressed. Moreover, overexpression of lncRNA WT1-AS blocked the PI3K/Akt/mTOR pathway. Upregulation of lncRNA WT1-AS or inhibition of the PI3K/Akt/mTOR pathway suppressed cancer cell migration in vitro, leading to cell cycle arrest, and promoted autophagy while inhibiting tumor growth <i>in vivo</i>. It also reduced the expression levels of Ki-67, MMP2, MMP9, and VEGF. The WT1-AS+rapamycin group was the most prominent in all experiments.</p><p><strong>Conclusion: </strong>The upregulation of lncRNA WT1-AS could suppress the PI3K/Akt/mTOR pathway, which inhibits cell migration and cell cycle arrest while promoting autophagy in gastric cancer cells.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 1","pages":"e18761429318398"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymol and Carvacrol as Potential Tocolytic and Anti-inflammatory Agents in Pregnant Rat Uterus.","authors":"Victor Manuel Muñoz-Pérez, Aurora Pérez-Sánchez, Andrés Salas-Casas A, Mario I Ortíz","doi":"10.2174/0118761429342128241231163610","DOIUrl":"10.2174/0118761429342128241231163610","url":null,"abstract":"<p><strong>Introduction: </strong>This work aimed to evaluate the anti-inflammatory and myorelaxant effect of thymol (TM) and carvacrol (CAR) in the pregnant rat uterus. Both compounds exhibit considerable antimicrobial, antispasmodic, and anti-inflammatory effects and due to these properties, they were studied in this in vitro model of premature birth induced by infection.</p><p><strong>Method: </strong>All uterine tissues were studied in uterine contraction tests to determine the inhibitory effect of TM, CAR (10, 56, 100, 150, and 230 μM), and nifedipine (a calcium channel antagonist) on phasic and tonic contraction induced by electro- and pharmacomechanical stimuli. The quantitative determination of cyclic adenosine monophosphate (cAMP) induced by TM and CAR in the uterine lysate was carried out by ELISA. For the determination of the anti-inflammatory effect of TM, the pro-inflammatory cytokine, interleukin (IL)-1β, in uterine samples stimulated with lipopolysaccharide (LPS) was measured. Forskolin (FSK) was used as a positive control to evaluate the cAMP and cytokine levels. TM, CAR, and nifedipine inhibited the uterine contractions at the highest concentration level, however, nifedipine was the most equipotent (p<0.05). In addition, TM and CAR did not increase the intracellular cAMP production in comparison with FSK (p<0.05). However, both compounds were able to decrease the LPS-induced production in a concentration-dependent manner that was considered statistically significant (p>0.05).</p><p><strong>Results: </strong>Finally, both the anti-inflammatory and uterine relaxing effects induced by TM and CAR were neither associated with the increase in cAMP levels nor with the production of IL-1β in pregnant rat uterine samples. Therefore, TM and CAR can be considered as alternative adjuvants for the treatment of infection-induced preterm labor. Before the in vitro experiments, an in-silico analysis was conducted using the Expaisy online server to evaluate the biological effects of thymol on uterine contraction.</p><p><strong>Conclusion: </strong>It is crucial to know the interaction and identification of genes encoding the Voltage-dependent L-type calcium channel subunit alpha-1C proteins, because of the functional relationship it may have in the inhibition of the uterine contraction. These properties place TM as a potentially safe and effective adjuvant agent in cases of preterm birth, an area of pharmacological treatment that requires urgent improvement.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429342128"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}