Phytotherapy Research最新文献

{"title":"Identification of Cannabidiolic and Cannabigerolic Acids as MTDL AChE, BuChE, and BACE-1 Inhibitors Against Alzheimer's Disease by In Silico, In Vitro, and In Vivo Studies.","authors":"Rosa Maria Vitale, Andrea Maria Morace, Antonio D'Errico, Federica Ricciardi, Antimo Fusco, Serena Boccella, Francesca Guida, Rosarita Nasso, Sebastian Rading, Meliha Karsak, Diego Caprioglio, Fabio Arturo Iannotti, Rosaria Arcone, Livio Luongo, Mariorosario Masullo, Sabatino Maione, Pietro Amodeo","doi":"10.1002/ptr.8369","DOIUrl":"https://doi.org/10.1002/ptr.8369","url":null,"abstract":"<p><p>Cannabidiolic (CBDA) and cannabigerolic (CBGA) acids are naturally occurring compounds from Cannabis sativa plant, previously identified by us as dual PPARα/γ agonists. Since the development of multitarget-directed ligands (MTDL) represents a valuable strategy to alleviate and slow down the progression of multifactorial diseases, we evaluated the potential ability of CBDA and CBGA to also inhibit enzymes involved in the modulation of the cholinergic tone and/or β-amyloid production. A multidisciplinary approach based on computational and biochemical studies was pursued on selected enzymes, followed by behavioral and electrophysiological experiments in an AD mouse model. The β-arrestin assay on GPR109A and qPCR on TRPM7 were also carried out. CBDA and CBGA are effective on both acetyl- and butyryl-cholinesterases (AChE/BuChE), as well as on β-secretase-1 (BACE-1) enzymes in a low micromolar range, and they also prevent aggregation of β-amyloid fibrils. Computational studies provided a rationale for the competitive (AChE) vs. noncompetitive (BuChE) inhibitory profile of the two ligands. The repeated treatment with CBDA and CBGA (10 mg/kg, i.p.) improved the cognitive deficit induced by the β-amyloid peptide. A recovery of the long-term potentiation in the hippocampus was observed, where the treatment with CBGA and CBDA also restored the physiological expression level of TRPM7, a receptor channel involved in neurodegenerative diseases. We also showed that these compounds do not stimulate GPR109A in β-arrestin assay. Collectively, these data broaden the pharmacological profile of CBDA and CBGA and suggest their potential use as novel anti-AD MTDLs.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epoxymicheliolide Reduces Radiation-Induced Senescence and Extracellular Matrix Formation by Disrupting NF-κB and TGF-β/SMAD Pathways in Lung Cancer.","authors":"Heng Zhou, Yong Chen, Ningzu Jiang, Yanxian Ren, Jiayuan Zhuang, Yue Ren, Lin Shen, Chenghao Li","doi":"10.1002/ptr.8352","DOIUrl":"10.1002/ptr.8352","url":null,"abstract":"<p><p>Lung cancer is a major cause of cancer-related mortality, and radiotherapy is often limited by tumor resistance and side effects. This study explores whether epoxymicheliolide (ECL), a compound from feverfew, can enhance radiotherapy efficacy in lung cancer. We tested ECL on A549 and PC-9 lung cancer cell lines to evaluate its effect on x-ray irradiation. We measured apoptosis, NF-κB pathway inhibition, TGF-β secretion reduction, and epithelial-mesenchymal transition suppression. In vivo, C57BL/6 mice with lung tumors received ECL and radiotherapy. ECL enhanced the antiproliferative effects of x-ray irradiation, induced apoptosis in senescent cells, inhibited the NF-κB pathway, reduced TGF-β levels, and suppressed epithelial-mesenchymal transition. ECL also inhibited tumor growth and improved survival in mice. ECL is a promising adjunct to radiotherapy for lung cancer, improving treatment outcomes by targeting multiple tumor progression mechanisms. It offers potential for enhanced management of lung cancer.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of Efficacy of Pomegranate Supplementation on Insulin Resistance and Sensitivity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Shao Yin, Fengya Zhu, Qian Zhou, Miao Chen, Xia Wang, Qiu Chen","doi":"10.1002/ptr.8362","DOIUrl":"https://doi.org/10.1002/ptr.8362","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The objective of this study is to assess the impact of pomegranate supplements on insulin resistance (IR) and insulin sensitivity through a systematic review and meta-analysis of randomized controlled trials (RCTs). Additionally, we aim to analyze the differences in efficacy among various pomegranate extracts and the sensitivity of different diseases to pomegranate supplementation. We conducted searches in PubMed, Embase, Web of Science, and Cochrane Library up to October 30, 2023, for relevant studies published in English. The treatment group required the intake of pomegranate extract for a minimum of 4 weeks, with no restrictions on the extract type. The control group received a placebo or a treatment excluding pomegranate extract. The primary outcome was homeostatic model assessment for insulin resistance (HOMA-IR) and fasting insulin (FI), and the secondary outcome was quantitative insulin sensitivity check index (QUICKI). RoB 2 was used to assess the risk of bias in the original studies. We pre-specified subgroup analyses based on types of intervention, intervention duration, health condition, and intervention dose. Sensitivity analysis was conducted to validate result stability, utilizing Begg's test and Egger's test for publication bias. Data synthesis and analysis were performed using Stata 15.1 software. This study included a total of 15 RCTs with 673 participants conducted in 7 countries. Risk of bias results indicated an overall low risk of bias of the articles. Participants included healthy individuals, overweight and obese individuals, non-alcoholic fatty liver disease (NAFLD) patients, type 2 diabetes (T2DM) patients, polycystic ovary syndrome (PCOS) patients, metabolic syndrome (MS) patients, and individuals with hyperlipidemia. Pomegranate extract variations included pomegranate juice (PJ), pomegranate seed oil (PSO) capsule, pomegranate/pomegranate peel (PP) extract capsule, and pomegranate peel-added bread. The control groups primarily received placebo treatments with varying dosage and frequency. No adverse reactions were reported in any of the studies. The summary results showed that compared to the control groups, pomegranate extract had no significant impact on improving HOMA-IR levels in participants (WMD = -0.03, 95%CI: -0.37 to 0.31, and p = 0.851) and FI (WMD = -0.03, 95%CI: -0.42 to 0.36, and p = 0.862). Additionally, there was no significant advantage of pomegranate extract on QUICKI changes in T2DM and PCOS patients (WMD = 0.00, 95%CI: 0.00 to 0.01, and p = 0.002). Subgroup analysis results indicated that pomegranate extract could improve HOMA-IR levels in PCOS patients (WMD = -0.42, 95%CI: -0.54 to -0.29, and p &lt; 0.001) and FI levels in T2DM, PCOS, and NAFLD patients. Our results indicate that pomegranate extract only improves HOMA-IR and FI levels in PCOS patients and FI levels in T2DM and NAFLD patients. No significant difference has been found for HOMA-IR, FI, or QUICKI in other metabolic diseases. The curre","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review of Antimicrobial Agents Against Clinically Important Bacterial Pathogens: Prospects for Phytochemicals.","authors":"Soumyadip Ghosh, Soumya Basu, Anand Anbarasu, Sudha Ramaiah","doi":"10.1002/ptr.8365","DOIUrl":"https://doi.org/10.1002/ptr.8365","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) hinders the effective treatment of a range of bacterial infections, posing a serious threat to public health globally, as it challenges the currently available antimicrobial drugs. Among the various modes of antimicrobial action, antimicrobial agents that act on membranes have the most promising efficacy. However, there are no consolidated reports on the shortcomings of these drugs, existing challenges, or the potential applications of phytochemicals that act on membranes. Therefore, in this review, we have addressed the challenges and focused on various phytochemicals as antimicrobial agents acting on the membranes of clinically important bacterial pathogens. Antibacterial phytochemicals comprise diverse group of agents found in a wide range of plants. These compounds have been found to disrupt cell membranes, inhibit enzymes, interfere with protein synthesis, generate reactive oxygen species, modulate quorum sensing, and inhibit bacterial adhesion, making them promising candidates for the development of novel antibacterial therapies. Recently, polyphenolic compounds have been reported to have proven efficacy against nosocomial multidrug-resistant pathogens. However, more high-quality studies, improved standards, and the adoption of rules and regulations are required to firmly confirm the clinical efficacy of phytochemicals derived from plants. Identifying potential challenges, thrust areas of research, and considering viable approaches is essential for the successful clinical translation of these compounds.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Polyphenols in Cellular Reversal of Patho-Mechanisms of Alzheimer's Disease Using In Vitro and In Vivo Models: A Comprehensive Review.","authors":"Monalisha Samal, Varsha Srivastava, Muzayyana Khan, Areeba Insaf, Naveen Reddy Penumallu, Aftab Alam, Bushra Parveen, Shahid Hussain Ansari, Sayeed Ahmad","doi":"10.1002/ptr.8344","DOIUrl":"https://doi.org/10.1002/ptr.8344","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is considered one of the most common neurological conditions associated with memory and cognitive impairment and mainly affects people aged 65 or above. Even with tremendous progress in modern neuroscience, a permanent remedy or cure for this crippling disease is still unattainable. Polyphenols are a group of naturally occurring potent compounds that can modulate the neurodegenerative processes typical of AD. The present comprehensive study has been conducted to find out the preclinical and clinical potential of polyphenols and elucidate their possible mechanisms in managing AD. Additionally, we have reviewed different clinical studies investigating polyphenols as single compounds or cotherapies, including those currently recruiting, completed, terminated, withdrawn, or suspended in AD treatment. Natural polyphenols were systematically screened and identified through electronic databases including Google Scholar, PubMed, and Scopus based on in vitro cell line studies and preclinical data demonstrating their potential for neuroprotection. A total of 63 significant polyphenols were identified. A multimechanistic pathway for polyphenol's mode of action has been proposed in the study. Out of 63, four potent polyphenols have been identified as promising potential candidates, based on their reported clinical efficacy. Polyphenols hold tremendous scope for the development of a future drug molecule as a phytopharmaceutical that may be incorporated as an adjuvant to the therapeutic regime. However, more high-quality studies with novel delivery methods and combinatorial approaches are required to overcome obstacles such as bioavailability and blood-brain barrier crossing to underscore the therapeutic potential of these compounds in AD management.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Ocimum basilicum L. Extract in Alleviating Autistic-Like Behaviors Induced by Maternal Separation Stress in Mice: Role of Neuroinflammation and Oxidative Stress.","authors":"Hossein Amini-Khoei, Nafiseh Taei, Hossein Tahmasebi Dehkordi, Zahra Lorigooini, Elham Bijad, Anahita Farahzad, Mohammad Rahimi Madiseh","doi":"10.1002/ptr.8360","DOIUrl":"https://doi.org/10.1002/ptr.8360","url":null,"abstract":"<p><p>A confluence of genetic, environmental, and epigenetic factors shapes autism spectrum disorder (ASD). Early-life stressors like MS play a contributing role in this multifaceted neurodevelopmental disorder. This research was to explore the efficacy of Ocimum basilicum L. (O.B.) extract in mitigating behaviors reminiscent of autism prompted by maternal separation (MS) stress in male mice, focusing on its impact on neuroinflammation and oxidative stress. MS mice were treated with O.B. extract at varying dosages (20, 40, and 60 mg/kg) from postnatal days (PND) 51-53 to PND 58-60. Behavioral experiments, including the Morris water maze, three-chamber test, shuttle box, and resident-intruder test, were conducted post-treatment. The method of maternal separation involved separating the pups from their mothers for 3 h daily, from PND 2 to PND 14. Molecular analysis of hippocampal tissue was performed to assess gene expression of Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Hippocampal and serum malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were measured. O.B. extract administration resulted in the amelioration of autistic-like behaviors in MS mice, as evidenced by improved spatial and passive avoidance memories and social interactions, as well as reduced aggression in behavioral tests. O.B. extract attenuated oxidative stress and neuroinflammation, as indicated by decreased MDA and increased TAC levels, as well as downregulation of TLR4, TNF-α, and IL-1β expression in the hippocampus. O.B. extract may offer a novel therapeutic avenue for ASD, potentially mediated through its anti-inflammatory and antioxidant properties.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of curcumin-piperine supplementation on lipid profile, glycemic index, inflammation, and blood pressure in patients with type 2 diabetes mellitus and hypertriglyceridemia.","authors":"Hanie Hosseini, Mohammad Bagherniya, Amirhossein Sahebkar, Bijan Iraj, Muhammed Majeed, Gholamreza Askari","doi":"10.1002/ptr.8304","DOIUrl":"10.1002/ptr.8304","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with insulin resistance and ensuing dysglycemia, dyslipidemia, and inflammation. Owing to the putative metabolic benefits of curcumin-piperine combination, we explored the efficacy of this combination in improving cardiometabolic indices of patients with T2DM and hypertriglyceridemia. In this double-blind clinical trial, 72 patients with T2DM and hypertriglyceridemia were randomized to receive either a tablet containing 500 mg of curcuminoids plus 5 mg of piperine, or a matched placebo for 12 weeks. Anthropometric indices, blood pressure, glycemic indices, lipid profile, C-reactive protein (CRP), quality of life, and mood were evaluated at baseline and end of the study. After 12 weeks of intervention, the levels of triglycerides (p-value = 0.001) and fasting blood glucose (p-value = 0.004) were significantly reduced in the curcumin-piperine compared with the placebo group. CRP levels were marginally reduced in the curcumin-piperine compared with the placebo group (p-value = 0.081). In addition, energy/fatigue significantly increased in the curcumin-piperine group compared to the control group (p-value = 0.024). However, between-group comparisons showed no significant change in other parameters, including anthropometric indices (waist circumference and body mass index (BMI)), biochemical parameters (low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c), and insulin), HOMA-IR, blood pressure, quality of life, and DASS-21 items between the studied groups (p-value >0.05). The current study showed that curcumin-piperine supplementation can improve serum CRP, triglycerides, and glucose concentrations in patients with T2DM and hypertriglyceridemia.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5150-5161"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-palmitoyl-d-glucosamine limits mucosal damage and VEGF-mediated angiogenesis by PPARα-dependent suppression of pAkt/mTOR/HIF1α pathway and increase in PEA levels in AOM/DSS colorectal carcinoma in mice.","authors":"Irene Palenca, Silvia Basili Franzin, Aurora Zilli, Luisa Seguella, Anna Troiani, Federico Pepi, Martina Vincenzi, Giuseppe Giugliano, Viviana Catapano, Italia Di Filippo, Giovanni Sarnelli, Giuseppe Esposito","doi":"10.1002/ptr.8303","DOIUrl":"10.1002/ptr.8303","url":null,"abstract":"<p><p>Chronic intestinal inflammation and neo-angiogenesis are interconnected in colorectal carcinoma (CRC) pathogenesis. Molecules reducing inflammation and angiogenesis hold promise for CRC prevention and treatment. N-Palmitoyl-d-glucosamine (PGA), a natural glycolipid analog with anti-inflammatory properties, has shown efficacy against acute colitis. Micronized PGA (mPGA) formulations exhibit superior anti-inflammatory activity. This study investigates the in vivo anti-angiogenic and protective effects of mPGA in a mouse model of colitis-associated CRC induced by azoxymethane/dextran sodium sulfate (AOM/DSS). CRC was induced in C57BL/6J mice using intraperitoneal azoxymethane followed by three cycles of 2.5% dextran sodium sulfate (DSS) in drinking water. Mice were treated with mPGA (30-150 mg/kg) with or without the PPARα inhibitor MK886 (10 mg/kg). At Day 70 post-azoxymethane injection, mice underwent anesthetized endoscopic colon evaluation. Post-mortem analysis of tumorigenesis and angiogenesis was performed using histological, immunohistochemical, and immunoblotting techniques. mPGA improved disease progression and survival rates in a dose- and PPARα-dependent manner in AOM/DSS-exposed mice. It reduced polyp formation, decreased pro-angiogenic CD31, pro-proliferative Ki67, and pro-inflammatory TLR4 expression levels, and inhibited VEGF and MMP-9 secretion by disrupting the pAkt/mTOR/HIF1α pathway. mPGA increased colon PEA levels, restoring anti-tumoral PPARα and wtp53 protein expression. Given its lack of toxicity, mPGA shows potential as a nutritional intervention to counteract inflammation-related angiogenesis in CRC.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5350-5362"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"SIRT1/AMPK and Akt/eNOS Signaling Pathways Are Involved in Endothelial Protection of Total Aralosides of Aralia elata (Miq) Seem Against High-Fat Diet-Induced Atherosclerosis in ApoE-/- Mice\".","authors":"","doi":"10.1002/ptr.8348","DOIUrl":"10.1002/ptr.8348","url":null,"abstract":"","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5533-5534"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geniposide modulates GSK3β to inhibit Th17 differentiation and mitigate endothelial damage in intracranial aneurysm.","authors":"Qian Zhang, Lu-Feng Shi, Run-Dong Chen, He-He Zhao, Cong Yu, Yi-Rong Wang, Peng Lu","doi":"10.1002/ptr.8320","DOIUrl":"10.1002/ptr.8320","url":null,"abstract":"<p><p>Intracranial aneurysm (IA) is a common cerebrovascular disease. Immune system disorders and endothelial dysfunction are essential mechanisms of its pathogenesis. This study aims to explore the therapeutic effect and mechanism of Geniposide (Gen) on IA, which has a protective impact on endothelial cells and cardiovascular and cerebrovascular diseases. IA mouse models were administered intraperitoneal injections of geniposide for 2 weeks following elastase injection into the right basal ganglia of the brain for intervention. The efficacy of Gen in treating IA was evaluated through pathological testing and transcriptome sequencing analysis of Willis ring vascular tissue. The primary mechanism of action was linked to the expression of GSK3β in Th17 cells. The percentage of splenic Th17 cell differentiation in IA mice was significantly inhibited by Gen. GSK3β/STAT3, and other pathway protein expression levels were also significantly inhibited by Gen. Additionally, TNF-α and IL-23 cytokine contents were significantly downregulated after Gen treatment. These results indicated that Gen significantly inhibited the percentage of Th17 cell differentiation, an effect that was reversed upon overexpression of the GSK3B gene. Furthermore, Gen-treated, Th17 differentiation-inducing cell-conditioned medium significantly up-regulated the expression of tight junction proteins ZO-1, Occludin, and Claudin-5 in murine aortic endothelial cells. Administering the GSK3β inhibitor Tideglusib to IA mice alleviated the severity of IA disease pathology and up-regulated aortic tight junction protein expression. In conclusion, Gen inhibits Th17 cell differentiation through GSK3β, which reduces endothelial cell injury and up-regulates tight junction protein expression.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"5184-5202"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}