Phytotherapy Research最新文献

{"title":"The Effect of Spirulina Supplementation on Blood Pressure in Adults: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Clinical Trials.","authors":"Hamidreza Shiri, Javad Yasbolaghi Sharahi, Maryam Alizadeh Sani, Seyyed Mohammad Javad Mousavi, Mohammad Hadi Nematollahi, Ali Akbar Soleimani, Jamal Amri, Ghodratollah Panahi","doi":"10.1002/ptr.8377","DOIUrl":"https://doi.org/10.1002/ptr.8377","url":null,"abstract":"<p><p>Previous studies have yielded controversial results regarding the effect of spirulina on blood pressure (BP), which need updating. So, this updated systematic review and meta-analysis of randomized controlled trials (RCTs) carry out a more accurate estimation of the effect of spirulina on BP in adults. This systematic searches (in PubMed/Medline, Scopus, and ISI Web of Science) until April 1, 2024, to identify related RCTs based on PICOS guidelines (population (individuals > 18 years old), the intervention (spirulina), the comparison (control or placebo group), the outcomes (systolic BP (SBP) and diastolic BP (DBP)), the study design (RCTs)), and PRISMA-checklist (Supporting Information, data S2). We evaluated the impact of spirulina on DBP and SBP. Conventional procedures were employed for analyzing publication bias, heterogeneity, and sensitivity. The GRADE criteria and the Cochrane assessment method were employed to evaluate the risk of bias (ROB) and certainty of evidence across the studies, respectively. The result shows spirulina consumption decreases SBP (WMD: -4.41 mmHg, 95% CI: -6.74 to -2.07, I² = 66.1%) and DBP (WMD: -2.84 mmHg, 95% CI: -4.65 to -1.03, I² = 62.3%). Subgroup analysis demonstrated SBP and DBP were still lower in individuals with ≥ 120 and ≥ 80 mmHg, hypertension (HTN) individuals, overweight individuals, age > 50 years, and > 8 weeks of intervention. Indeed, we do not observe publication bias, ROB, or interference studies in the overall results of BPs, and based on GRADE, our outcomes have moderate quality. Because of the low number of studies and participants, the dose-response and meta-regression are not significant. His study demonstrated spirulina intervention decreased SBP and DBP in HTN and overweight individuals, age > 50 years, and > 8 weeks of intervention. So, spirulina intake decreases BP and could be used in clinical practice. Furthermore, more and high-quality RCTs are needed to establish the clinical efficacy of the spirulina and determine cutoff spirulina interventions based on dose and duration. Trial Registration: PROSPERO: CRD42024534608.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625911","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":"Mushrooms and Colorectal Cancer: Unveiling Mechanistic Insights and Therapeutic Innovations.","authors":"Samridhi Kurl, Snimmer Kaur, Neeraj Mittal, Gurpreet Kaur","doi":"10.1002/ptr.8382","DOIUrl":"https://doi.org/10.1002/ptr.8382","url":null,"abstract":"<p><p>Nature has bestowed us with an abundant reservoir of resources that besides having nutritional value, are prolific mines of bioactive constituents with a plethora of medicinal activities. Mushrooms have been used since centuries in traditional system of medicine for their purported health benefits including anticancer activities. Thorough research, spanning over centuries in Japan, China, Korea, and the USA, has established the unique properties of mushrooms and their extractives in the prevention and treatment of various types cancer. The aim of the review article is to provide a comprehensive overview of the existing literature highlighting the potential relationship between mushrooms and colorectal cancer. Different databases such as PubMed, Web of Science, Google Scholar, and ScienceDirect were searched and a total of 62 articles and two book chapters were reviewed, and data were extracted. Multiple studies have demonstrated that mushrooms exhibit anticancer activities, effectively reducing adverse side effects such as nausea, myelosuppression, anemia, and sleeplessness. Furthermore, they have been shown to mitigate drug resistance following chemotherapy and radiation therapy. Certain species such as Antrodia, Pleurotus, Ganoderma, Lentinula, Hericium, Cantharellus, Clitocybe, Coprinopsis, Trametes, Sparassis, Lactarius, and so on manifest anticancer activity in colon. The article can help improve the scientific understanding of the co-relationship between mushrooms and colorectal cancer. This may help in advancing the research directions and integrating the mushroom-based strategies into current treatment protocols of colorectal cancer.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625529","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 Chinese Herbal Medicine and Underlying Mechanism for the Treatment of Myocardial Infarction.","authors":"Jiaojiao Pan, Jinhui Wang, Ziwen Lei, He Wang, Nan Zeng, Junbo Zou, Xiaofei Zhang, Jing Sun, Dongyan Guo, Fei Luan, Yajun Shi","doi":"10.1002/ptr.8368","DOIUrl":"https://doi.org/10.1002/ptr.8368","url":null,"abstract":"<p><p>Myocardial infarction (MI) is a prevalent disease with high mortality rates worldwide. The course of MI is intricate and variable, necessitating personalized treatment strategies based on different mechanisms. However, variety of postoperative complications and rejections, such as heart failure, arrhythmias, cardiac rupture, and left ventricular thrombus, contribute to a poor prognosis. Despite the inclusion of antiplatelet agents and statins in the conventional treatment regimen, their clinical applicability is constrained by potential adverse effects and limited efficacy. Additionally, the mechanisms leading to MI are complex and diverse. Therefore, the development of novel compounds for MI treatment. The use of traditional Chinese medicine (TCM) in the prevention and treatment of cardiovascular diseases, including MI, is grounded in its profound historical background, comprehensive theoretical system, and accumulated knowledge. An increasing number of contemporary evidence-based medical studies have demonstrated that TCM plays a significant role in alleviating symptoms and improving the quality of life for MI patients. Chinese herbal formulations and active ingredients can intervene in the pathological process of MI through key factors such as inflammation, oxidative stress, apoptosis, ferroptosis, pyroptosis, myocardial fibrosis, angiogenesis, and autophagy. This article critically reviews existing herbal formulations from an evidence-based medicine perspective, evaluating their research status and potential clinical applications. Additionally, it explores recent advancements in the use of herbal medicines and their components for the prevention and treatment of MI, offering detailed insights into their mechanisms of action.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625917","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":"Oxyberberine Inhibits Hepatic Gluconeogenesis via AMPK-Mediated Suppression of FoxO1 and CRTC2 Signaling Axes.","authors":"Fan Wu, Fuer Lu, Hui Dong, Meilin Hu, Lijun Xu, Dingkun Wang","doi":"10.1002/ptr.8381","DOIUrl":"https://doi.org/10.1002/ptr.8381","url":null,"abstract":"<p><p>Oxyberberine (OBB), a natural metabolite of berberine, has been shown to exhibit inhibitory effects on gluconeogenesis in our previous work. This work was designed to investigate the potential effects and underlying mechanisms of OBB on hepatic gluconeogenesis. Our work found that OBB significantly inhibited the expressions of glucose 6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), and decreased the glucose production in palmitic acid-induced HepG2 cells. Then, AMPK/Akt/FoxO1 and AMPK/CRTC2 signaling pathways were confirmed by transcriptomics and network pharmacology analyses. It was shown that AMPK activation may phosphorylate and promote nuclear exclusion of FoxO1 and CRTC2, two key regulators of hepatic gluconeogenesis transcriptional pathways, resulting in the inhibition of gluconeogenesis under OBB administration. Afterwards, AMPK/Akt/FoxO1, AMPK/CRTC2 signaling pathways were evidenced by western blot, immunoprecipitation and confocal immunofluorescence, and the targeted inhibitor (Compound C) and siRNA of AMPK were applied for further mechanism verification. Moreover, it was found that OBB treatment activated AMPK/Akt/FoxO1 and AMPK/CRTC2 signaling pathways to decrease hepatic gluconeogenesis in db/db mice. Similarly, the in vivo inhibitory effects of OBB on gluconeogenesis were also diminished by AMPK inhibition. Our work demonstrated that OBB can inhibit hepatic gluconeogenesis in vitro and in vivo, and its underlying mechanisms were associated with AMPK-mediated suppression of FoxO1 and CRTC2 signaling axes.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625487","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":"Linarin Identified as a Bioactive Compound of Lycii Cortex Ameliorates Insulin Resistance and Inflammation Through the c-FOS/ARG2 Signaling Axis.","authors":"Wenxuan Liu, Runlin Gui, Yang Li, Man Li, Zhen Lei, Yanyan Jin, Yi Yu, Yujia Li, Lu Qian, Yuyan Xiong","doi":"10.1002/ptr.8370","DOIUrl":"https://doi.org/10.1002/ptr.8370","url":null,"abstract":"<p><p>Insulin resistance (IR) is a central pathophysiological process underlying numerous chronic metabolic disorders, including type 2 diabetes and obesity. Lycii Cortex, a widely used traditional Chinese herb, has demonstrated potential benefits in preventing and managing diabetes and IR. Whereas, the specific bioactive compounds responsible for these protective effects and their underlying mechanisms of action remain elusive. This study aimed to identify the bioactive components within Lycii Cortex that contribute to its anti-diabetic effects and to elucidate the molecular mechanisms underlying its beneficial actions on insulin resistance. Network pharmacology and molecular docking analyses were employed to identify the potential active compounds in Lycii Cortex and their corresponding target proteins. An in vitro model of IR was established using palmitic acid (PA)-treated HepG2 cells. Cell viability was assessed using the CCK-8 assay, while glucose uptake was evaluated by 2-NBDG staining and extracellular glucose measurement. To validate the in vitro findings, an in vivo model of obesity-induced IR was established using high-fat diet (HFD)-fed mice. The network pharmacology analysis preliminarily identified 13 candidate chemicals and 10 hub LyC and IR-related genes (LIRRGs). Molecular docking analysis demonstrates that Linarin as the potential active component exhibits the greatest potential to target c-FOS for preventing obesity-induced IR. Enrichment analysis suggested that Linarin-targeted pathways are correlated with inflammation. In vitro experimental validation demonstrated that Linarin was capable of protecting against PA-induced IR in HepG2 cells evidenced by improving glucose uptake ability and reducing extracellular glucose content. Additionally, we found that Linarin ablated PA-induced increase in the expression of c-FOS and inflammatory cytokines. Furthermore, in PA-treated cells, silencing c-FOS markedly improved glucose consumption, and reduced inflammation and Arginase 2 (ARG2) expression. Similarly, as exposure to PA, silencing ARG2 also ameliorated glucose uptake and inflammation, while not affecting c-FOS expression. In vivo experiments further showed that Linarin administration remarkably improved glucose tolerance and insulin sensitivity, and reduced the fat mass and body weight in HFD-induced obese mice. In this study, Linarin has been identified as the bioactive compound of Lycii Cortex to ameliorate obesity-related IR and inflammation through the c-FOS/ARG2 signaling cascade. These findings underscore the therapeutic potential of Linarin and provide valuable insights into developing novel intervention strategies for type 2 diabetes therapy.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625406","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":"Tanshinone IIA Alleviates Pulmonary Fibrosis by Inhibiting Pyroptosis of Alveolar Epithelial Cells Through the MAPK Signaling Pathway.","authors":"Yong Xu, Yi-Ran Wang, Wen-Pan Peng, Hui-Min Bu, Yao Zhou, Qi Wu","doi":"10.1002/ptr.8372","DOIUrl":"https://doi.org/10.1002/ptr.8372","url":null,"abstract":"<p><p>The current dearth of safe and efficacious pharmaceutical interventions for pulmonary fibrosis (PF) has prompted investigations into alternative treatments. This study aim to investigate the underlying mechanisms of Tanshinone IIA in the treatment of PF. PF was induced in a mouse model by intratracheal infusion of bleomycin (BLM), followed by gavage administration of varying concentrations of Tanshinone IIA. Lung tissue was obtained for pathological slides, proteomic and transcriptomic analyses. The target was predicted and analyzed using network pharmacology. Initially, an in vitro model in A549 cells was established by adding BLM, followed by treatment with varying concentrations of Tanshinone IIA. Subsequently, NAC and the ERK inhibitor, U0126, were individually introduced. Treatment with Tanshinone IIA in vivo decreased lung tissue lesions. Proteomic, transcriptomic, and network pharmacology analyses suggested that Tanshinone IIA may offer therapeutic benefits for PF by mitigating oxidative stress damage via the MAPK signaling pathway. In vitro studies demonstrated that BLM treatment in A549 cells induced exposure of the N-terminal end of the pyroptosis core protein GSDMD, and elevated oxidative stress levels in A549 cells, concomitant with the upregulation of P-ERK protein expression. Subsequent administration of Tanshinone IIA, NAC, and U0126 reduced the number of A549 cells undergoing pyroptosis, decreased oxidative stress levels, and decreased P-ERK protein expression. These findings suggested that Tanshinone IIA potentially delays the progression of PF. The mechanism of action involves the inhibition of oxidative stress and reduced epithelial cell pyroptosis via the MAPK-related pathway. The findings may provide a new reference for treatment of PF.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625898","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":"Epigenetic Effects of Natural Products in Inflammatory Diseases: Recent Findings.","authors":"Qianyi Yao, Tanjun Wei, Hongmei Qiu, Yongqing Cai, Lie Yuan, Xin Liu, Xiaoli Li","doi":"10.1002/ptr.8364","DOIUrl":"https://doi.org/10.1002/ptr.8364","url":null,"abstract":"<p><p>Inflammation is an essential step for the etiology of multiple diseases. Clinically, due to the limitations of current drugs for the treatment of inflammatory diseases, such as serious side effects and expensive costs, it is urgent to explore novel mechanisms and medicines. Natural products have received extensive attention recently because of their multi-component and multi-target characteristics. Epigenetic modifications are crucial pathophysiological targets for developing innovative therapies for pharmacological interventions. Investigations examining how natural products improving inflammation through epigenetic modifications are emerging. This review state that natural products relieve inflammation via regulating the gene transcription levels through chromosome structure regulated by histone acetylation levels and the addition or deletion of methyl groups on DNA duplex. They could also exert anti-inflammatory effects by modulating the proteins in typical inflammatory signaling pathways by ubiquitin-related degradation and the effect of glycolysis derived free glycosyls. Studies on epigenetic modifications have the potential to facilitate the development of natural products as therapeutic agents. Future research directed at better understanding of how natural products modulate inflammatory processes through less studied epigenetic modifications including neddylation, SUMOylation, palmitoylation and lactylation, may provide new implications. Meanwhile, higher quality preclinical studies and more powerful clinical evidence are still needed to firmly establish the clinical efficacy of the natural products. Trial Registration: ClinicalTrials.gov Identifier: NCT01764204; ClinicalTrials.gov Identifier: NCT05845931; ClinicalTrials.gov Identifier: NCT04657926; ClinicalTrials.gov Identifier: NCT02330276.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605928","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":"Natural Products in the Prevention of Degenerative Bone and Joint Diseases: Mechanisms Based on the Regulation of Ferroptosis.","authors":"Kuanhui Gao, Longlong Lv, Zhichao Li, Chenmoji Wang, Jiahao Zhang, Daodi Qiu, Haipeng Xue, Zhanwang Xu, Guoqing Tan","doi":"10.1002/ptr.8366","DOIUrl":"https://doi.org/10.1002/ptr.8366","url":null,"abstract":"<p><p>Degenerative bone and joint diseases (DBJDs), characterized by osteoporosis, osteoarthritis, and chronic inflammation of surrounding soft tissues, are systemic conditions primarily affecting the skeletal system. Ferroptosis, a programmed cell death pathway distinct from apoptosis, autophagy, and necroptosis. Accumulating evidence suggests that ferroptosis is intricately linked to the pathogenesis of DBJDs, and targeting its regulation could be beneficial in managing these conditions. Natural products, known for their anti-inflammatory and antioxidant properties, have shown unique advantages in preventing DBJDs, potentially through modulating ferroptosis. This article provides an overview of the latest research on ferroptosis, with a focus on its role in the pathogenesis of DBJDs and the therapeutic potential of natural products targeting this cell death pathway, offering novel insights for the prevention and treatment of DBJDs.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605856","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":"Red Yeast Rice or Lovastatin? A Comparative Evaluation of Safety and Efficacy Through a Multifaceted Approach.","authors":"Giovanna Rigillo, Giulia Baini, Renato Bruni, Giulia Puja, Elisabetta Miraldi, Luca Pani, Fabio Tascedda, Marco Biagi","doi":"10.1002/ptr.8371","DOIUrl":"https://doi.org/10.1002/ptr.8371","url":null,"abstract":"<p><p>The increasing use of red yeast rice (RYR) as a natural supplement to manage blood cholesterol levels is driven by its active compound, monacolin K (MK), which is chemically identical to the statin drug lovastatin (LOV). Despite its growing popularity, concerns persists regarding the safety and efficacy of RYR compared to pure statins. This study aimed to evaluate the phytochemical composition, pharmacological effects, and safety profile of various RYR samples in comparison with LOV. RYR samples with different MK content were analyzed using HPLC-DAD to quantify monacolins and other bioactive compounds. The inhibitory activity on HMG-CoA reductase was assessed through an enzymatic assay, while pharmacokinetic properties were predicted using in vitro simulated digestion and in silico models. In vitro cytotoxicity was evaluated in intestinal, hepatic, renal, and skeletal muscle cell models. Additionally, the transcriptional levels of muscle damage-related target genes were evaluated by qRT-PCR in skeletal muscle cells treated with a selection of RYR samples. Significant variability in the phytochemical composition of RYR samples was observed, particularly in the content of secondary monacolins, triterpenes, and polyphenols. The RYR phytocomplex exhibited superior inhibition of HMG-CoA reductase activity compared to isolated LOV, suggesting synergistic effects between secondary monacolins and other compounds. Molecular insights revealed that RYR samples had a lower impact on muscle cells than LOV, as reflected also by cell viability. These findings suggest that RYR could serve as a safe alternative to purified statins. However, further research is needed to fully elucidate the mechanisms behind the synergistic activity of the phytocomplex and to firmly establish the clinical efficacy of this natural product.</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":"142605859","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":"Tetrandrine Alleviates Pulmonary Fibrosis by Modulating Lung Microbiota-Derived Metabolism and Ameliorating Alveolar Epithelial Cell Senescence.","authors":"Jinzhong Zhuo, Lanhe Chu, Dongyu Liu, Jinming Zhang, Weimou Chen, Haohua Huang, Qi Yu, Xiaojin Meng, Fei Zou, Shaixi Cai, Hangming Dong","doi":"10.1002/ptr.8374","DOIUrl":"https://doi.org/10.1002/ptr.8374","url":null,"abstract":"<p><p>Tetrandrine (TET) is a minimally toxic drug extracted from the root of Stephania tetrandra. We previously demonstrated that TET could ameliorate pulmonary fibrosis (PF) by modulating autophagy. However, the mechanism behind TET's protective effects on PF remains unclear. In this study, we utilized 16S rRNA gene sequencing, nontargeted metabolomic analysis, and network pharmacology to identify changes in lung microbiota and metabolites that mediate alveolar epithelial cell senescence in bleomycin (BLM)-induced PF in mice. Additionally, we employed Western blot analysis, RT-PCR, and immunofluorescence staining to investigate the in vitro and in vivo effects of TET and its influential bacterial metabolites on PF. The TET intervention alleviated PF by regulating the compositions of lung microbial communities (Streptococcus, Micrococcus, Acinetobacter, Altererythrobacter, Atopostipes, Candidatus Cloacimonas, Clostridium sensu stricto 1, Sphingomonas, Listeria, Blautia, and Pseudomonas) and metabolites (3,4-dihydroxyphenylpropionic acid (3,4-DHPPA), 6-Aminonicotinamide, N-acetyl-5-methoxykynuramine, and resiniferatoxin). Through network pharmacological analysis, it was determined that 3,4-DHPPA played a crucial role in alleviating PF by further inhibiting the senescence of alveolar epithelial cells, a finding further validated in ex vivo experiments. TET mitigated BLM-induced PF in murine models through the modulation of lung microbiota composition and metabolism. Specifically, TET augmented the level of the microbiota-derived metabolite, 3,4-DHPPA, which in turn attenuated alveolar epithelial cell senescence.</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":"142605861","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}