{"title":"Polyphenols in clinical trials: Current trends.","authors":"Francisco Alejandro Lagunas-Rangel","doi":"10.1002/ptr.8313","DOIUrl":"https://doi.org/10.1002/ptr.8313","url":null,"abstract":"","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110849","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}
Anupam Bishayee, Amanda Penn, Neha Bhandari, Riley Petrovich, Lindsay K DeLiberto, Jack T Burcher, Sandra Maria Barbalho, Siddavaram Nagini
{"title":"Dietary plants for oral cancer prevention and therapy: A review of preclinical and clinical studies.","authors":"Anupam Bishayee, Amanda Penn, Neha Bhandari, Riley Petrovich, Lindsay K DeLiberto, Jack T Burcher, Sandra Maria Barbalho, Siddavaram Nagini","doi":"10.1002/ptr.8293","DOIUrl":"https://doi.org/10.1002/ptr.8293","url":null,"abstract":"<p><p>Oral cancer is a disease with high mortality and rising incidence worldwide. Although fragmentary literature on the anti-oral cancer effects of plant products has been published, a comprehensive analysis is lacking. In this work, a critical and comprehensive evaluation of oral cancer preventative or therapeutic effects of dietary plants was conducted. An exhaustive analysis of available data supports that numerous dietary plants exert anticancer effects, including suppression of cell proliferation, viability, autophagy, angiogenesis, invasion, and metastasis while promoting cell cycle arrest and apoptosis. Plant extracts and products target several cellular mechanisms, such as the reversal of epithelial-to-mesenchymal transition and the promotion of oxidative stress and mitochondrial membrane dysfunction by modulation of various signaling pathways. These agents were also found to regulate cellular growth signaling pathways by action on extracellular signal-regulated kinase and mitogen-activated protein kinase, inflammation via modulation of cyclooxygenase (COX)-1, COX-2, and nuclear factor-κB p65, and metastasis through influence of cadherins and matrix metalloproteinases. In vivo studies support these findings and demonstrate a decrease in tumor burden, incidence, and hyperplastic and dysplastic changes. Clinical studies also showed decreased oral cancer risk. However, high-quality studies should be conducted to establish the clinical efficacy of these plants. Overall, our study supports the use of dietary plants, especially garlic, green tea, longan, peppermint, purple carrot, saffron, tomato, and turmeric, for oral cancer prevention and intervention. However, further research is required before clinical application of this strategy.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081286","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}
Xiang Zheng, Fang-Chen Ye, Tao Sun, Fei-Jun Liu, Ming-Jian Wu, Wen-Hao Zheng, Ling-Feng Wu
{"title":"Delay the progression of glucocorticoid-induced osteoporosis: Fraxin targets ferroptosis via the Nrf2/GPX4 pathway.","authors":"Xiang Zheng, Fang-Chen Ye, Tao Sun, Fei-Jun Liu, Ming-Jian Wu, Wen-Hao Zheng, Ling-Feng Wu","doi":"10.1002/ptr.8310","DOIUrl":"https://doi.org/10.1002/ptr.8310","url":null,"abstract":"<p><p>Glucocorticoid-induced osteoporosis (GIOP) commonly accelerates bone loss, increasing the risk of fractures and osteonecrosis more significantly than traditional menopausal osteoporosis. The extracellular environment influenced by glucocorticoids heightens fracture and osteonecrosis risks. Fraxin (Fra), a key component of the traditional Chinese herbal remedy Cortex Fraxini, is known for its wide-ranging pharmacological effects, but its impact on GIOP remains unexplored. This investigation aims to delineate the effects and underlying mechanisms of Fra in combating dexamethasone (Dex)-induced ferroptosis and GIOP. We established a mouse model of GIOP via intraperitoneal injections of Dex and cultured osteoblasts with Dex treatment for in vitro analysis. We evaluated the impact of Fra on Dex-treated osteoblasts through assays such as C11-BODIPY and FerroOrange staining, mitochondrial functionality tests, and protein expression analyses via Western blot and immunofluorescence. The influence of Fra on bone microarchitecture of GIOP in mice was assessed using microcomputerized tomography, hematoxylin and eosin staining, double-labeling with Calcein-Alizarin Red S, and immunohistochemistry at imaging and histological levels. Based on our data, Fra prevented Dex-induced ferroptosis and bone loss. In vitro, glutathione levels increased and malondialdehyde, lipid peroxidation, and mitochondrial reactive oxygen species decreased. Fra treatment also increases nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and COL1A1 expression and promotes bone formation. To delve deeper into the mechanism, the findings revealed that Fra triggered the activation of Nrf2/GPX4 signaling. Moreover, the use of siRNA-Nrf2 blocked the beneficial effect of Fra in osteoblasts cultivated with Dex. Fra effectively combats GIOP by activating the Nrf2/GPX4 signaling pathway to inhibit ferroptosis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081258","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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-08-24","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}
Hanie Hosseini, Mohammad Bagherniya, Amirhossein Sahebkar, Bijan Iraj, Muhammed Majeed, Gholamreza Askari
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-08-20","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":"Multiple health outcomes associated with algae and its extracts supplementation: An umbrella review of systematic reviews and meta-analyses.","authors":"Caixia Wang, Ruixue Min, Qilun Zhou, Yue Qi, Yanli Ma, Xiaofeng Zhang","doi":"10.1002/ptr.8305","DOIUrl":"https://doi.org/10.1002/ptr.8305","url":null,"abstract":"<p><p>Algae and its extracts, widely consumed as functional foods, offer numerous health benefits; however, a comprehensive systematic summary of clinical evidence is currently lacking. The study was to assess the available evidence and provide an accurate estimate of the overall effects of algae and its extracts supplementation on various health outcomes. The comprehensive searches in PubMed, Scopus, Embase, Web of Science, and the Cochrane Library until December 22, 2023 were implemented. The random-effects model was employed to pool the overall effect sizes (ESs) and the corresponding 95% confidence intervals (CIs) using Stata software. Moreover, detecting the methodological quality and evidence level of the eligible studies were employed by A Measurement Tool to Assess Systematic Review 2 (AMSTAR2) and the Grading of Recommendations Assessment Development and Evaluation. Ultimately, 25 articles covering 133 health outcomes were included in this umbrella review. The pooled results demonstrated that the algae and its extracts could significantly decrease body weight (ES = -1.65; 95% CI: -1.97, -1.34; p < 0.001), body mass index (BMI) (ES = -0.42; 95% CI: -0.78, -0.07; p = 0.020), waist circumference (WC) (ES = -1.40; 95% CI: -1.40, -1.39; p < 0.001), triglyceride (TG) (ES = -1.38; 95% CI: -2.15, -0.62; p < 0.001), total cholesterol (TC) (ES: -1.40; 95% CI: -2.09, -0.72; p < 0.001), very low-density lipoprotein cholesterol (VLDL-C) (ES = -7.85; 95% CI: -8.55, -7.15; p < 0.001), fasting blood glucose (ES = -2.68; 95% CI: -4.57, -0.79; p = 0.005), glycated hemoglobin (HbA1c) (ES = -0.15; 95% CI: -0.24, -0.07; p < 0.001), systolic blood pressure (ES = -3.21; 95% CI: -5.25, -1.17; p = 0.002), diastolic blood pressure (ES = -3.84; 95% CI: -7.02, -0.65; p = 0.018), alanine transaminase (ES = -0.42; 95% CI: -0.70, -0.14; p = 0.003), and alkaline phosphatase (ES = -0.54; 95% CI: -0.99, -0.10; p = 0.017). Due to the limited number of studies, no benefit was displayed on markers of inflammation and oxidative stress. Considering the suboptimal quality of studies and the insufficient articles pertaining to certain outcomes, further well-designed research is imperative to substantiate the observed findings.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004995","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":"Harmine promotes megakaryocyte differentiation and thrombopoiesis by activating the Rac1/Cdc42/JNK pathway through a potential target of 5-HTR2A.","authors":"Xiaoxi Liu, Jia Lai, Xiaoqin Zhang, Anguo Wu, Ling Zhou, Yueyue Li, Qianqian Huang, Xinwu Huang, Hua Li, Cai Lan, Jian Liu, Feihong Huang, Jianming Wu","doi":"10.1002/ptr.8317","DOIUrl":"https://doi.org/10.1002/ptr.8317","url":null,"abstract":"<p><p>Harmine (HM), a β-carboline alkaloid extracted from plants, is a crucial component of traditional Chinese medicine (TCM) known for its diverse pharmacological activities. Thrombocytopenia, a common and challenging hematological disorder, often coexists with serious illnesses. Previous research has shown a correlation between HM and thrombocytopenia, but the mechanism needs further elucidation. The aim of this study was to clarify the mechanisms underlying the effects of HM on thrombocytopenia and to develop new therapeutic strategies. Flow cytometry, Giemsa staining, and Phalloidin staining were used to assess HM's impact on Meg-01 and HEL cell differentiation and maturation in vitro. A radiation-induced thrombocytopenic mouse model was employed to evaluate HM's effect on platelet production in vivo. Network pharmacology, molecular docking, and protein blotting were utilized to investigate HM's targets and mechanisms. The results demonstrated that HM dose-dependently promoted Meg-01 and HEL cell differentiation and maturation in vitro and restored platelet levels in irradiated mice in vivo. Subsequently, HM was found to be involved in the biological process of platelet production by upregulating the expressions of Rac1, Cdc42, JNK, and 5-HTR2A. Furthermore, the targeting of HM to 5-HTR2A and its correlation with downstream Rac1/Cdc42/JNK were also confirmed. In conclusion, HM regulates megakaryocyte differentiation and thrombopoiesis through the 5-HTR2A and Rac1/Cdc42/JNK pathways, providing a potential treatment strategy for thrombocytopenia.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996306","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}
Xirui He, Xufei Chen, Yan Yang, Jingyi Gu, Yulu Xie, Yujie Liu, Man Hao, Michael Heinrich
{"title":"The role of gastrodin in the management of CNS-related diseases: Underlying mechanisms to therapeutic perspectives.","authors":"Xirui He, Xufei Chen, Yan Yang, Jingyi Gu, Yulu Xie, Yujie Liu, Man Hao, Michael Heinrich","doi":"10.1002/ptr.8314","DOIUrl":"https://doi.org/10.1002/ptr.8314","url":null,"abstract":"<p><p>Central nervous system (CNS)-related diseases have a high mortality rate, are a serious threat to physical and mental health, and have always been an important area of research. Gastrodin, the main active metabolite of Gastrodia elata Blume, used in Chinese medicine and food, has a wide range of pharmacological effects, mostly related to CNS disorders. This review aims to systematically summarize and discuss the effects and underlying mechanisms of gastrodin in the treatment of CNS diseases, and to assess its potential for further development as a lead drug in both biomedicine and traditional Chinese medicine. Studies on the pharmacological effects of gastrodin on the CNS indicate that it may exert anti-neurodegenerative, cerebrovascular protective, and ameliorative effects on diabetic encephalopathy, perioperative neurocognitive dysfunction, epilepsy, Tourette's syndrome, depression and anxiety, and sleep disorders through various mechanisms. To date, 110 gastrodin products have been approved for clinical use, but further multicenter clinical case-control studies are relatively scarce. Preclinical studies have confirmed that gastrodin can be used to treat CNS-related disorders. However, important concerns need to be addressed in the context of likely non-specific, assay interfering effects when gastrodin is studied using in vitro and in silico approaches, calling for a systematic assessment of the evidence to date. High-quality clinical trials should have priority to evaluate the therapeutic safety and clinical efficacy of gastrodin. Further experimental research using appropriate in vivo models is also needed, focusing on neurodegenerative diseases, cerebral ischemic and hypoxic diseases, brain damage caused by methamphetamine or heavy metals, and epilepsy.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988569","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":"Ginsenoside Re inhibits non-small cell lung cancer progression by suppressing macrophage M2 polarization induced by AMPKα1/STING positive feedback loop.","authors":"Xiaoyu Tang, Man Zhu, Zeren Zhu, Wenjun Tang, Hongmei Zhang, Yanbin Chen, Feng Liu, Yanmin Zhang","doi":"10.1002/ptr.8309","DOIUrl":"https://doi.org/10.1002/ptr.8309","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC) promote tumor cell metastasis by interacting with cancer cells. Ginsenoside Re is capable of modulating the host immune system and exerts anticancer effects through multiple pathways. Both AMPK and STING are involved in the regulation of MΦ polarization, thereby affecting tumor progression. However, whether there is a regulatory relationship between them and its effect on MΦ polarization and tumor progression is unclear. The aim of this study was to provide mechanistic evidence that ginsenoside Re modulates MΦ phenotype through inhibition of the AMPKα1/STING positive feedback loop and thus exerts an antimetastatic effect in NSCLC immunotherapy. Cell culture models and conditioned media (CM) systems were constructed, and the treated MΦ were analyzed by database analysis, RT-PCR, Western blotting, flow cytometry, and immunofluorescence to determine the regulatory relationship between AMPK and STING and the effects of ginsenoside Re on MΦ polarization and tumor cells migration. The effects of ginsenoside Re (10, 20 mg/kg/day) on TAMs phenotype as well as tumor progression in mice were assessed by HE staining, immunohistochemical staining, and Western blotting. In this study, AMPKα1/STING positive feedback loop in NSCLC TAMs induced M2 type polarization, which in turn promoted NSCLC cell migration. In addition, ginsenoside Re was discovered to inhibit M2-like MΦ polarization, thereby inhibiting NSCLC cell migration. Mechanistically, Re was able to inhibit the formation of the AMPKα1/STING positive feedback loop, thereby inhibiting its induction of M2-like MΦ and consequently inhibiting the epithelial-mesenchymal transition (EMT) process of NSCLC cells. Furthermore, in mouse models, Re was found to suppress LLC tumor growth and colonization by inhibiting M2-type polarization of TAMs. Our finding indicates that ginsenoside Re can effectively modulate MΦ polarization and thus play an important role in antimetastatic immunotherapy of NSCLC.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907371","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":"Neutrophil extracellular traps: Potential targets for the treatment of rheumatoid arthritis with traditional Chinese medicine and natural products.","authors":"Yuan Liu, Yuan Qu, Chuanguo Liu, Di Zhang, Bing Xu, Yakun Wan, Ping Jiang","doi":"10.1002/ptr.8311","DOIUrl":"https://doi.org/10.1002/ptr.8311","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Abnormal formation of neutrophil extracellular traps (NETs) at the synovial membrane leads to the release of many inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Elastase, histone H3, and myeloperoxidase, which are carried by NETs, damage the soft tissues of the joints and aggravate the progression of RA. The balance of NET formation coordinates the pro-inflammatory and anti-inflammatory effects and plays a key role in the development of RA. Therefore, when NETs are used as effector targets, highly targeted drugs with fewer side effects can be developed to treat RA without damaging the host immune system. Currently, an increasing number of studies have shown that traditional Chinese medicines and natural products can regulate the formation of NETs through multiple pathways to counteract RA, which shows great potential for the treatment of RA and has a promising future for clinical application. In this article, we review the latest biological progress in understanding NET formation, the mechanism of NETs in RA, and the potential targets or pathways related to the modulation of NET formation by Chinese medicines and natural products. This review provides a relevant basis for the use of Chinese medicines and natural products as natural adjuvants in the treatment of RA.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894097","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}