Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"RETRACTION: Diosmetin Exerts Cardioprotective Effect on Myocardial Ischaemia Injury in Neonatal Rats by Decreasing Oxidative Stress and Myocardial Apoptosis","authors":"","doi":"10.1111/1440-1681.70009","DOIUrl":"10.1111/1440-1681.70009","url":null,"abstract":"<p>\u0000 <b>RETRACTION</b>: <span>G. Mo</span>, <span>Y. He</span>, <span>X. Zhang</span>, <span>X. Lei</span> and <span>Q. Luo</span>, “ <span>Diosmetin Exerts Cardioprotective Effect on Myocardial Ischaemia Injury in Neonatal Rats by Decreasing Oxidative Stress and Myocardial Apoptosis</span>,” <i>Clinical and Experimental Pharmacology and Physiology</i> <span>47</span>, no. <span>10</span> (<span>2020</span>): <span>1713</span>–<span>1722</span>, https://doi.org/10.1111/1440-1681.13309.\u0000 </p><p>The above article, published online on 27 March 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Yang Yang; and John Wiley &amp; Sons Australia, Ltd. Following publication, the authors notified the journal of significant issues affecting the validity and integrity of their findings. They acknowledged that several data points for oxidative stress markers and myocardial apoptosis levels were inconsistent with the original laboratory records. Following our own analysis, further concerns were identified. Specifically, the actin bands shown in the western blot in Figure 1D and the P65, p-P65, and p-AKT bands in Figure 5A were found to be duplicated in other articles. The authors did not respond to our requests for comments on these additional issues. The editors have deemed the results and conclusions of this article invalid.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trimetazidine restores autophagy via lncRNA H19/AMPK in diabetic heart: Implications for its therapeutic value against diabetic cardiomyopathy","authors":"Wei Wei,&nbsp;Yadi Hu,&nbsp;Jing Gao,&nbsp;Danjun Fan,&nbsp;Xiaorong Ye,&nbsp;Yan Chen","doi":"10.1111/1440-1681.70006","DOIUrl":"10.1111/1440-1681.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Previous studies have shown that trimetazidine (TMZ) alleviates diabetes-induced cardiac dysfunction. However, the underlying mechanism for its protective effects on cardiac function remains incompletely understood. Diminished autophagy was found in diabetic hearts, and restoration of autophagy generates cardioprotective effect. This study aims to investigate whether and how TMZ produces protective effect through increasing autophagic activity in the diabetic heart.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A high-fat diet and low-dose streptozotocin were applied to induce type 2 diabetes mellitus (T2DM) in male C57BL/6 mice, followed by treatment with TMZ for 14 weeks before cardiac function was evaluated. To mimic the diabetic condition, the neonatal rat cardiomyocytes (NRCMs) were exposed to high glucose/palmitic acid (HP) in the presence or absence of TMZ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that TMZ treatment promotes autophagic flux in cardiomyocytes, which is impaired in diabetes. We further found that the AMPK and lncRNA H19 played critical roles in mediating TMZ-induced enhancement of autophagy in cardiomyocyte. We showed that TMZ treatment restored the level of H19 and phosphorylated AMPK (p-AMPK T172) in diabetic heart and NRCMs exposed to HP. Of note, the effect of TMZ on autophagy and p-AMPK was abolished by knockdown of H19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings indicated that TMZ is able to recover the cardiac autophagic activity which is impaired by T2DM, and the underlying mechanism accounted for this ability is mostly likely attributed to the restored expression of H19 and AMPK activity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667398","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":"Disability status investigation and risk prediction model for middle-aged and older adults in Anhui Province: A derivation and validation study","authors":"Jing Li,&nbsp;Shu Wang,&nbsp;Yan-Bei Zhang","doi":"10.1111/1440-1681.70005","DOIUrl":"10.1111/1440-1681.70005","url":null,"abstract":"<p>This study investigated the disability status of middle-aged and older adults in Anhui Province, China, with a primary focus on physical disability, and constructed a nomogram to predict disability risk. Data was collected through a province-wide questionnaire survey conducted in 16 cities and counties from January to December 2021, involving 3386 participants aged 60 years and above. The abilities of daily living (ADL) scale assessed participants' comprehensive ability. Risk factors for disability were identified using least absolute shrinkage and selection operator and logistic regression, highlighting six independent factors: age, poor sleep quality, depression, malnutrition, stroke, and the number of comorbid chronic diseases. A nomogram prediction model was then established and validated internally and externally. The model demonstrated good fit according to the Hosmer–Lemeshow test and provided significant benefits across various thresholds, as shown by decision curve analysis. This nomogram accurately and quickly identifies high-risk groups, aiding in early intervention.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667349","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":"Effect of Bacillus clausii in attenuating symptoms of DSS-induced ulcerative colitis by modulating NFkB pathway and oxidative stress in mice","authors":"Syeda Rida Zainab,&nbsp;Jehan Zeb Khan,&nbsp;Mujeeb Ur Rehman,&nbsp;Fawad Ali Shah,&nbsp;Muhammad Khalid Tipu","doi":"10.1111/1440-1681.70004","DOIUrl":"10.1111/1440-1681.70004","url":null,"abstract":"<p>Ulcerative colitis (UC) is a condition characterized by inflammation and ulcer formation in the colon and rectum due to genetic and environmental factors. It is a common condition, with a global prevalence rate exceeding 0.3%. Current treatments have limited efficacy and can cause unwanted side effects, leading to a high recurrence rate and reduced quality of life for patients. This study suggests that <i>Bacillus clausii</i> has a beneficial role in reducing intestinal inflammation and relieving colitis symptoms in mice. The study aimed to examine <i>B. clausii</i>'s potential to reduce the progression and pathogenesis of dextran sulphate sodium (DSS)–induced UC. <i>Bacillus clausii</i> was administered to mice as a pre-treatment, post-treatment and adjunct treatment with sulfasalazine for 14 days. The study found that <i>B. clausii</i> effectively reduced the severity of colitis in mice when used preventatively. Administering <i>B. clausii</i> after the onset of colitis also effectively alleviated symptoms. Combining <i>B. clausii</i> with standard sulfasalazine as adjunct therapy was more effective in reducing intestinal inflammation than using a single therapy alone. <i>B. clausii</i> has shown the potential to prevent colon damage and decrease the likelihood and severity of the disease. Immunohistochemistry results revealed a decrease in the expression of pro-inflammatory cytokines such as IL-1β, TNF-α and NFkB in colon tissue. Additionally, mice that received <i>B. clausii</i> showed a significant increase in anti-oxidant levels and improved haematological markers. In conclusion, it must be emphasized that <i>B. clausii</i> possesses the potential to alleviate the symptoms of UC.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603448","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":"An evodiamine derivative inhibits osteoclast differentiation and protects against OVX-induced bone loss in mice","authors":"Chao Liu,&nbsp;Huaxing Shen,&nbsp;Huang Li,&nbsp;Nan Wang,&nbsp;Shipeng He,&nbsp;Guangming Ye,&nbsp;Wei Cong","doi":"10.1111/1440-1681.13926","DOIUrl":"10.1111/1440-1681.13926","url":null,"abstract":"<p>Evodiamine is a biologically active alkaloid extracted from the fruit of the traditional Chinese medicine <i>Evodia rutaecarpa</i> (Juss.) Benth. (Fructus Evodiae, Wuzhuyu). However, due to its lipophilic chemical structure, low water solubility results in poor bio-availability, which limits its broader application. 3-Amino-10-hydroxyl-evodiamine (E2) was a water-soluble derivative of evodiamine with good anti-tumour bioactivity previously developed by our team; however, its anti-osteoporosis activity remains unclear. This study demonstrates that E2 inhibits the maturation of osteoclasts and bone resorption promoted by receptor activator of nuclear factor-κB ligand (RANKL). Mechanistically, E2 reduced RANKL-induced activation of nuclear factor kappa B (NF-κB) as well as mitogen-activated protein kinase (MAPK) pathways, causing the suppression of the expression of genes associated with osteoclasts in vitro. These genes included nuclear factor of activated T cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), cathepsin k (CTSK) and dendritic cell–specific transmembrane protein (DC-STAMP). Treatment with E2 in vitro resulted in the attenuation of p-ERK, p-JNK, p-p38 and NFATc1 levels. Furthermore, ovariectomized (OVX) mice treated with E2 showed a decrease in osteoclast formation as well as preservation of bone mass. This study concludes with evidence that E2 decreases osteoclast maturation and bone resorption through the regulation of multiple signalling pathways, thereby exhibiting an osteoprotective role in OVX mice. Consequently, E2 exhibits significant potential as a prospective drug candidate for treating osteoporosis.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575489","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":"Short-term exercise counteracts accelerated ageing impacts on physical performance and liver health in mice","authors":"Ana P. Pinto,&nbsp;Vitor R. Muñoz,&nbsp;Maria Eduarda A. Tavares,&nbsp;Ivo V. de Sousa Neto,&nbsp;Jonathas R. dos Santos,&nbsp;Guilherme S. Rodrigues,&nbsp;Ruither O. Gomes Carolino,&nbsp;Luciane C. Alberici,&nbsp;Fernando M. Simabuco,&nbsp;Giovana R. Teixeira,&nbsp;José R. Pauli,&nbsp;Leandro P. de Moura,&nbsp;Dennys E. Cintra,&nbsp;Eduardo R. Ropelle,&nbsp;Ellen C. Freitas,&nbsp;Donato A. Rivas,&nbsp;Adelino S. R. da Silva","doi":"10.1111/1440-1681.70001","DOIUrl":"10.1111/1440-1681.70001","url":null,"abstract":"<p>Senescence impairs liver physiology, mitochondrial function and circadian regulation, resulting in systemic metabolic dysregulation. Given the limited research on the effects of combined exercise on an ageing liver, this study aimed to evaluate its impact on liver metabolism, circadian rhythms and mitochondrial function in senescence-accelerated mouse-prone 8 (SAMP8) and senescence-accelerated mouse-resistant 1 (SAMR1) mice. Histological, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunoblotting analyses were conducted, supplemented by transcriptomic data sets and AML12 hepatocyte studies. Sedentary SAMP8 mice exhibited decreased muscle strength, reduced mitochondrial complex I levels and increased lipid droplet accumulation. In contrast, combined exercise mitigated muscle strength loss, upregulated proteins involved in mitochondrial complexes (CIII, CIV, CV) and increased <i>Bmal1</i> messenger RNA (mRNA) expression in the liver. These molecular adaptations are associated with healthier liver phenotypes and may influence metabolic function and cellular longevity. Notably, elevated lipid content in aged mice was reduced post-exercise, indicating liver benefits even after a relatively short intervention. The combined exercise regimen did not improve aerobic capacity, likely due to the low volume and brief duration of running. Moreover, no significant effects were observed in SAMR1 mice, possibly because the training intensity was insufficient for younger, healthier animals. These findings underscore the potential of combined strength and endurance exercise to attenuate age-related liver dysfunction, particularly in ageing populations.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544086","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":"GLP-1 receptor agonist liraglutide alleviates kidney injury by regulating nuclear translocation of NRF2 in diabetic nephropathy","authors":"Tingting Lin,&nbsp;Yuze Zhang,&nbsp;Qifeng Wei,&nbsp;Zugui Huang","doi":"10.1111/1440-1681.70003","DOIUrl":"10.1111/1440-1681.70003","url":null,"abstract":"<p>Diabetic nephropathy (DN) is a severe renal disorder that arises as a complication of diabetes. Liraglutide, an analogue of a glucagon-like peptide 1 (GLP-1) receptor agonist, has been shown to decrease diabetes-caused renal damage. Nevertheless, the complete understanding of the roles and mechanism remains unclear. In our study, diabetic rat models were created through a single intraperitoneal injection of streptozotocin (STZ). The level of fasting blood glucose, 24-h urine protein, serum creatinine (Scr) and blood urea nitrogen (BUN) were assessed. Periodic acid-Schiff (PAS) staining was applied to examine the pathological changes in renal tissues. Reactive oxygen species (ROS) formation was measured via dichloro-dihydro-fluorescein diacetate (DCFH-DA) probes. Western blot was conducted to examine the levels of oxidative stress-related and extracellular matrix (ECM)-associated proteins. The nuclear translocation of NRF2 was investigated through immunofluorescence and Western blot assays. We demonstrated that liraglutide attenuated DN-induced oxidative stress and ECM deposition in vitro and in vivo. Liraglutide exerted a reno-protective effect by promoting nuclear translocation of NRF2 in mesangial cells. ML385, an NRF2 inhibitor, counteracted the beneficial impact of liraglutide.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544085","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":"Odoratin balances ROS/NO through EZH2/PPARγ signalling to improve myocardial fibrosis","authors":"Bin Rao,&nbsp;Min Zhang,&nbsp;Min Liu,&nbsp;Yan Tu","doi":"10.1111/1440-1681.70002","DOIUrl":"10.1111/1440-1681.70002","url":null,"abstract":"<p>Myocardial fibrosis is a critical concern in clinical medicine. This study explores the potential of odoratin as a treatment for myocardial fibrosis and investigates its underlying mechanisms. In vitro experiments involved stimulating primary mouse cardiomyocytes with TGF-β1, followed by odoratin treatment, to assess levels of reactive oxygen species (ROS) and nitric oxide (NO). In vivo, a mouse model of myocardial fibrosis was established using abdominal aortic constriction (AAC) and treated with odoratin. ROS and NO levels in myocardial tissue were then evaluated. Immunofluorescence and Western blotting analysis showed that odoratin reduced excess ROS, enhanced NO production and decreased fibrosis-related protein expression in vitro. In vivo, odoratin significantly improved cardiac function, reduced ROS, increased NO levels and mitigated fibrosis in AAC-induced mice. Both in vitro and in vivo, odoratin inhibited the expression of NADPH oxidase 4 and EZH2, while promoting the expression of phosphorylated endothelial nitric oxide synthase (p-eNOS) and PPARγ. The anti-fibrotic effects of odoratin were reversed by PPARγ antagonism, and EZH2 overexpression diminished PPARγ activation by odoratin. These findings suggest that odoratin may combat myocardial fibrosis by balancing ROS and NO through PPARγ activation, with EZH2 inhibition likely playing a key regulatory role.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496167","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":"Caffeic acid phenethyl ester ameliorates colistin-induced nephrotoxicity in rats via modulation of FOXO1/Nrf2/Sirt1 axis","authors":"Mohammed Z. Nasrullah,&nbsp;Thikryat Neamtalllah,&nbsp;Mohannad Alshibani,&nbsp;Alaa A. Bagalagel,&nbsp;Ahmad O. Noor,&nbsp;Hussain T. Bakhsh,&nbsp;Ashraf B. Abdel-Naim","doi":"10.1111/1440-1681.70000","DOIUrl":"10.1111/1440-1681.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colistin (Cst) is one of the antimicrobial peptides and is reserved for use against multi-drug-resistant Gram-negative bacteria. However, the clinical value of Cst is limited by its nephrotoxic adverse effects. Caffeic acid phenethyl ester (CAPE) is a honeybee propolis flavonoid recognised for its diverse pharmacological potential. It has demonstrated d antioxidant and anti-inflammatory properties, as well as protective effects against chemically induced toxicity in variuos biological systems. This study aimed to investigate the impact of CAPE on nephrotoxicity induced in rats by Cst.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Animals were randomly divided into five groups. Group 1 served as control, group 2 received CAPE (10 mg/kg) orally, group 3 received Cst IP, group 4 received Cst + CAPE (5 mg/kg) and group 5 received Cst + CAPE (10 mg/kg). All treatments were given daily for 10 consecutive days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CAPE notably attenuated Cst-inducednephrotoxicity as shown by reducing urea serum levels, creatinine, cystatin C, urinary protein contents and urinary N-acetyl-β-D-glucosaminidase (NAG). This was confirmed by histological investigations that indicated amelioration of histopathological changes in the kidney architecture as well as the deposition of collagen in renal tissues. CAPE exhibited antioxidant effects supported by the prevention of rise in Cst-induced lipid peroxidation and depletion of superoxide dismutase and catalase enzymatic activities. In addition, CAPE inhibited the expression of the inflammatory markers including tumour necrosis factor-α, nuclear factor kappa B and interleukin-6. These actions were associated with modulation of messenger ribonucleic acid (mRNA) expression of <i>Bax</i> and <i>Bcl-2</i> in favour of anti-apoptosis. CAPE inhibited Cst-induced rise in forkhead box O1 (FOXO1) expression and downregulation of nuclear factor erythroid 2–related factor 2 (Nrf2) and Sirtuin 1 (Sirt1) immune-expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CAPE protects against nephrotoxicity induced by Cst in ratsprimarily through its antioxidant, antiinflammatory and antiapoptotic activities. These pritective effects are mediated via modulation of FOXO1/Nrf2/Sirt1 axis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496165","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":"Gross saponins of Tribulus terrestris attenuate rheumatoid arthritis by promoting apoptosis of fibroblast-like synoviocytes and reducing inflammation by inhibiting MAPK signalling pathway","authors":"Xinghai Cheng,&nbsp;Yuantao Su,&nbsp;Ningzheng Dong,&nbsp;Meng Liu,&nbsp;Mengting Wang,&nbsp;Tiantian Zhou,&nbsp;Haibin Zhou","doi":"10.1111/1440-1681.13925","DOIUrl":"10.1111/1440-1681.13925","url":null,"abstract":"<p>Among the numerous treatment options for rheumatoid arthritis (RA), the promotion of synoviocyte apoptosis and inhibition of inflammation are considered the most effective. However, the potential pro-apoptotic effects of gross saponins of <i>Tribulus terrestris</i> (GSTT), which are natural saponins derived from the herb <i>Tribulus terrestris</i> L., on rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and their essential molecular mechanisms remain unclear. The aim of the present study was to investigate the influence of different concentrations of GSTT on RA-FLSs using various assays, including cell counting kit-8 (CCK-8), reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and western blot analysis. These assessments were conducted to evaluate the cell viability, changes in the levels of inflammatory cytokines, apoptosis rates and alterations in protein expression related to this process. In vivo, arthritis clinical score, haematoxylin and eosin (HE) staining and ELISA were used to assess paw inflammation, histopathology and serum inflammatory cytokine changes. Our findings demonstrated that GSTT substantially promotes the apoptosis of RA-FLSs and reduces pro-inflammatory cytokine levels. GSTT also reduced the Bcl-2/Bax ratio and inhibited JNK and p38 phosphorylation. Furthermore, GSTT exhibits positive effects on RA by improving clinical scores, reducing synovial inflammatory infiltration and lowering serum pro-inflammatory cytokine levels. Therefore, by promoting the apoptosis of RA-FLSs and suppressing inflammation through the inhibition of the MAPK signalling pathway, GSTT is a promising therapeutic intervention for RA.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496166","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}