Phytomedicine最新文献

{"title":"Rosavin derived from Rhodiola alleviates colitis in mice through modulation of Th17 differentiation.","authors":"Yi Wang, Yu Jiang, Mingxing Li, Yaqin Xiao, Qianyun Zhao, Jiuping Zeng, Shulin Wei, Shuhan Chen, Yueshui Zhao, Fukuan Du, Yu Chen, Shuai Deng, Jing Shen, Xiaobing Li, Wanping Li, Fang Wang, Yuhong Sun, Li Gu, Zhangang Xiao, Shengpeng Wang, Xu Wu","doi":"10.1016/j.phymed.2024.156318","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156318","url":null,"abstract":"<p><strong>Background: </strong>Rosavin (RSV) is a naturally occurring compound isolated from Rhodiola species. While RSV has been reported with pharmacological activities of anti-oxidation, anti-inflammation, anti-stress and immunomodulation, its effect on colitis and the underlying mechanisms remain unclear.</p><p><strong>Purpose: </strong>This study aims to investigate whether and how RSV alleviated colitis in mice.</p><p><strong>Study design and methods: </strong>The protective effect of RSV (50, 100, 200 mg/kg, p.o.) was investigated in dextran sulfate sodium (DSS) mediated mouse models of acute and chronic colitis. Alterations in fecal microbiota were evaluated by 16S rRNA sequencing. Pseudo germ-free mice achieved by antibiotics treatment were applied to assess the RSV-mediated functional role of gut microbiota in colitis. RNA sequencing was performed to determine RSV-induced colonic response. Primary T cell culture was conducted to examine the effect of RSV on Th17 and Treg differentiation. Whole blood assay, dual luciferase reporter assay, and molecular docking methods were applied to investigate the mechanisms and targets of RSV in Th17 regulation.</p><p><strong>Results: </strong>Oral RSV significantly relieved DSS-mediated acute and chronic colitis in mice, which recovered body weight loss, reduced disease activity index, alleviated colon injury, inhibited inflammation, suppressed the apoptosis of intestinal epithelia, and maintained intestinal barrier function. Moreover, RSV specifically regulated intestinal microbiota by recovering DSS-mediated microbial changes and elevating beneficial microbes such as Lactobacillus and Akkermansia. Antibiotics treatment experiment showed that the protective role of RSV was at least partially dependent on gut microbiota; however, in vitro incubation showed that RSV did not directly promote the growth of Lactobacillus and Akkermansia strains. Further analysis showed that RSV-mediated genetic alterations in colon were enriched in pathways related to lymphocyte regulation. Additionally, RSV regulated the balance of Th17/Treg in colitis mice. Importantly, RSV inhibited the differentiation of Th17 cell in vitro, suppressed the production of IL-17 by Th17 cells, and downregulated Rorc encoding RORγt and its downstream Il17. RSV significantly inhibited the RORγt transcription activity and bound to its ligand binding domain.</p><p><strong>Conclusion: </strong>RSV alleviates murine colitis through regulating intestinal immunity. Notably, RSV is identified as a novel regulator of Th17 cells that inhibits RORγt-mediated Th17 differentiation. These findings potentiate the Rhodiola-derived natural chemicals as novel anti-colitis agents.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156318"},"PeriodicalIF":6.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pimpinellin mitigates DSS-induced ulcerative colitis in mice by reducing inflammation and regulating gut microbiota.","authors":"Bin Lv, Lu Hou, Haolong Zhang, Cuiting Hao, Zheyu Song","doi":"10.1016/j.phymed.2024.156308","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156308","url":null,"abstract":"<p><strong>Background: </strong>Pimpinellin is a phenylpropanoid compound involved in various physiological and pathological processes in the body. The specific impact of pimpinellin on ulcerative colitis (UC) remains uncertain. Research on pimpinellin by using a dextran sulfate sodium (DSS)-induced UC model can lay the groundwork for future drug screening and various treatment approaches for UC.</p><p><strong>Purpose and methods: </strong>This research focused on investigating the effects and mechanisms of pimpinellin on DSS-induced UC in mice.</p><p><strong>Results: </strong>The findings indicated that pimpinellin mitigated DSS-induced shortening of the colon and intestinal barrier damage and notably lowered inflammatory cytokine levels. Mechanistic analysis revealed that pimpinellin boosted the protein expression of intestinal barrier proteins by inhibiting the MAPK/NF-κB signaling pathway. Additionally, pimpinellin enhanced the levels of beneficial gut probiotics (S24-7 and Lactobacillaceae) while reducing the presence of harmful bacteria (Enterobacteriaceae). Further studies indicated that administering 100 mg/kg pimpinellin could significantly alleviate UC by modulating the gut microbiota.</p><p><strong>Conclusion: </strong>In summary, timely use of pimpinellin can alleviate DSS-induced UC by reducing inflammation, maintaining intestinal barrier integrity, and adjusting gut microbiota. This research broadens the potential pharmaceutical applications of pimpinellin.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156308"},"PeriodicalIF":6.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sesquiterpene lactone from Artemisia argyi inhibited cancer proliferation by inducing apoptosis and ferroptosis via key cell metabolism enzyme NDUFA4.","authors":"Ziling Wang, Zhouyuan Li, Rongsheng Ji, Wenjing Wang, Jing Li, Wenli Xu, Xiaoxuan Li, Xiaolong Yang, Hongzhi Du, Dahui Liu","doi":"10.1016/j.phymed.2024.156312","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156312","url":null,"abstract":"<p><strong>Background: </strong>Artemisia argyi is a well-known medicinal plant. A. argyi has been widely used in clinical for about 3000 years, owing to its extensive pharmacological activity. Among these, its anti-cancer properties are the most reported activity. However, its pharmacodynamic compounds remain unknown.</p><p><strong>Purpose: </strong>This study aimed to investigate the potential anti-cancer compounds in A. argyi and reveal its molecular mechanisms and targets.</p><p><strong>Methods: </strong>Firstly, A. argyi were extracted with 70 % ethanol, yielding A. argyi EtOH (AAE) crude extracts. AAE was extracted with Ethyl acetate and Butanol successively to yield A. argyi EtOAc (AAEA) and A. argyi Butanol (AAB) sub-fraction. And, AAE, AAEA, and AAB were prepared to assess their anti-cancer ability in vitro and in vivo. Then, the natural products were isolated from active sub-fraction via activity-oriented separation and identification. Meanwhile, all the compounds were evaluated the anti-cancer effect. The anti-proliferation mechanism of representative compounds was explored, based on programmed cell death. Moreover, 4D-data-independent (DIA) quantitative proteomic studies were performed to reveal the underlying targets and mechanism of representative compounds. Finally, the pharmacodynamic compound and key target interaction were identified by the evaluation of targets function, molecular docking, surface plasmon resonance (SPR) assay, and small interfering RNA. In addition, the toxicity of pharmacodynamic compounds were evaluated by in vitro and zebrafish model in vivo.</p><p><strong>Results: </strong>AAEA demonstrated stronger inhibitory effects than AAB on various cancer cell lines in vitro. And, AAEA sub-fraction effectively inhibited the tumor growth in vitro and in vivo. Subsequently, we isolated and identified 47 anti-cancer components from AAEA, especially 23 of which were isolated from A. argyi for the first time. Among them, 8 sesquiterpenes compounds showed strong anti-cancer activity. Moreover, compound 3 (moxartenolide) exhibited stronger induction of apoptosis and ferroptosis. Ultimately, a series of studies based on proteomics revealed that Moxartenolide inhibited cancer cell proliferation through the key enzyme NDUFA4. In addition, toxicological evaluation in vivo and in vitro demonstrated the safety of the candidate drug.</p><p><strong>Conclusion: </strong>These findings reveal the anti-cancer components of A. argyi based on activity-oriented separation and identification for the first time. Specially, Compound 3 (moxartenolide) inhibited cancer proliferation by inducing apoptosis and ferroptosis via key cell metabolism enzyme NDUFA4. Briefly, it suggests that A. argyi has the potential of anti-cancer drug development.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156312"},"PeriodicalIF":6.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asiaticoside alleviated NAFLD by activating Nrf2 and inhibiting the NF-κB pathway.","authors":"Yunfei Wei, Yibo Zhang, Baihe Zhan, Yajie Wang, Jiaqi Cheng, Hao Yu, Mengfan Lv, Yanmin Zhang, Yaxin Zhai, Yuan Guan, Haihua Feng","doi":"10.1016/j.phymed.2024.156317","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156317","url":null,"abstract":"<p><strong>Background: </strong>Nonalcoholic fatty liver disease (NAFLD) is a globally prevalent clinical problem of chronic liver disorder whose main pathogenic mechanisms are hepatic lipid accumulation, oxidative stress, and inflammatory reactions. Asiaticoside (Asi) is a compound derived from Centella asiatica, possesses antioxidant, antiphlogistic, antifibrotic, as well as wound healing properties.</p><p><strong>Purpose: </strong>The aim of this study was to investigate the effects of Asi on NAFLD and its potential mechanisms.</p><p><strong>Study design: </strong>Two versions of experimental models were constructed using free fatty acids (FFAs)-stimulated HepG2 cells along with high-fat diet (HFD)-incited NAFLD in mice.</p><p><strong>Methods: </strong>The pivotal action of Nrf2 was then explored using Ml-385 or Nrf2^-/- mice.</p><p><strong>Results: </strong>The results indicated that Asi activated the Nrf2 to alleviate oxidative stress, inhibited the NF-κB to reduce the inflammatory response, and notably decreased lipid droplets and alleviated steatosis.</p><p><strong>Conclusion: </strong>In conclusion, Asi demonstrates a potential to activate Nrf2 as well as inhibit the NF-κB pathway, there alleviate NAFLD.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156317"},"PeriodicalIF":6.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total saponins from Panax japonicus mediate the paracrine interaction between adipocytes and macrophages to promote lipolysis in the adipose tissue during aging via the NLRP3 inflammasome/GDF3/ATGL axis.","authors":"Fangqi Xia, Yaqi Hu, Yaqi Wang, Mengzhen Xue, Leiqi Zhu, Yuanyang Li, Yifan Zhang, Shuwen Wang, Rui Wang, Qi Yuan, Yumin He, Ding Yuan, Jihong Zhang, Chengfu Yuan","doi":"10.1016/j.phymed.2024.156304","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156304","url":null,"abstract":"<p><p>Adipocytic lipolysis is strongly related to the increase of visceral fat, decrease of exercise capacity, and various other metabolic syndromes during aging. It is significantly influenced by the paracrine relationship between adipocytes and the adipose tissue macrophages (ATMs), and the cytokines secreted by ATMs have endocrine effects on adjacent tissues. We previously reported that the total saponins from Panax japonicus (TSPJs) can enhance lipid metabolism. In this work, we for the first time proved that TSPJs promoted adipocytic lipolysis by preventing NLRP3 activation in ATMs to inhibit the expression of GDF3. The decrease of GDF3 by TSPJs restored the expression of the adipose triglyceride lipase (ATGL) and phosphorylated hormone-sensitive lipase (p-HSL), both of which are known to decrease with aging. Thus, the NLRP3 inflammasome/GDF3/ATGL axis may be a worthy target in developing future clinical solutions for aging-related obesity.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156304"},"PeriodicalIF":6.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of Dachaihu decoction for sepsis: A randomized controlled trial.","authors":"Na Huang, Yat Hoi Tam, Zhitong Zhang, Xingyu Kao, Zhen Yang, Weixian Xu, Kang Yuan, Mingfeng He, Jingli Chen","doi":"10.1016/j.phymed.2024.156311","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156311","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a critical condition characterized by multi-organ dysfunction (MODS) that presents significant treatment challenges. Traditional Chinese medicine (TCM), particularly Dachaihu decoction (DCH), has shown potential in addressing sepsis-related complications.</p><p><strong>Purpose: </strong>To comprehensively evaluate the efficacy and safety of DCH in the treatment of sepsis.</p><p><strong>Methods: </strong>Eligible septic patients were randomly assigned to either the DCH or control group in a 1:1 ratio. The intervention course lasted for 3 days. Primary outcomes were 28-day all-cause mortality, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Secondary outcomes were assessed through various clinical parameters, including: (1) inflammatory markers; (2) liver function indices; (3) renal function markers; (4) gastrointestinal function metrics and (5) coagulation parameters.</p><p><strong>Results: </strong>70 septic patients were included in the full analysis set. No significant difference in 28-day all-cause mortality was observed between the control and DCH groups (10 (28.6 %) vs. 9 (25.7 %), p = 0.788). However, DCH significantly reduced SOFA score (-3.0 (interquartile range, IQR, -5.5, -2.0) vs. 0.0 (IQR, -3.5, 0.0), p = 0.025), APACHE II score (-4.0 (IQR, -8.0, -2.0) vs. 0.0 (IQR, -2.0, 2.0), p < 0.001), aspartate transaminase (-12.70 (IQR, -76.15, -3.35) vs. 2.40 (IQR, -8.05, 10.55), p = 0.001), total bilirubin (-2.30 (IQR, -7.45, 3.62) vs. 1.80 (IQR, -2.35, 11.25), p = 0.028), acute gastrointestinal injury grade (R¯, 26.04 vs. 44.96, p < 0.001), gastrointestinal dysfunction score (-5.0 (IQR, -6.0, -2.5) vs. -1.0 (IQR, -2.0, 0.5), p < 0.001), serum intestinal fatty acid-binding protein (-334.5 (IQR, -375.4, -288.8) vs. -34.8 (IQR, -104.2, -34.0), p < 0.001), and increased citrulline levels (6.97 (IQR, 6.76, 7.62) vs. 0.70 (IQR, -1.30, 2.83), p < 0.001), and also inhibiting platelet loss (-2.0 (IQR, -30.5, 45.5) vs. -26.0 (IQR, -65.0, 9.5), p = 0.043). Additionally, DCH demonstrated improvements in inflammation, renal function, and coagulation, with fewer serious adverse events reported in the DCH group (2.44 % vs. 7.32 %, p = 0.305).</p><p><strong>Conclusion: </strong>DCH is both effective and safe in treating septic MODS. Nonetheless, further research is required to refine study designs and enhance outcomes for septic patients.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156311"},"PeriodicalIF":6.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phillygenin improves diabetic nephropathy by inhibiting inflammation and apoptosis via regulating TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β signaling pathways.","authors":"Qi Feng, Xiaoyue Yu, Junwei Xie, Fengxun Liu, Xiaonan Zhang, Shiyang Li, Yixue Wang, Shaokang Pan, Dongwei Liu, Zhangsuo Liu","doi":"10.1016/j.phymed.2024.156314","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156314","url":null,"abstract":"<p><strong>Background: </strong>Phillygenin (PHI), a main bioactive compound found in the fruit of Forsythia suspensa, exhibits antiviral, antioxidant, anti-inflammatory, and antihypertensive activities. However, the molecular mechanisms underlying its effects on diabetic nephropathy (DN) remain unclear.</p><p><strong>Purpose: </strong>To evaluate the therapeutic effects of PHI on DN and elucidate the molecular mechanisms involved.</p><p><strong>Methods: </strong>Cell viability assays and RNA-seq analyses were performed to identify potential mechanisms through which PHI regulates HG-induced MPCs. The therapeutic efficacy of PHI was assessed in both DN cells and mouse models. Cytokine levels were measured using ELISA, while the expression levels of key signaling pathways, including TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β along with downstream effectors were analyzed via immunoblotting, immunofluorescence, and immunohistochemical staining.</p><p><strong>Results: </strong>PHI inhibited inflammatory responses and alleviated apoptosis by reducing the expression levels of IL-6, TNF-α, IL-1β, TLR4, MyD88, NF-κB, and cleaved caspase-3, while enhancing the phosphorylation of PI3K, AKT, GSK3β (Ser9), and pro-caspase-3 in MPCs under HG conditions in vitro. Additionally, in vivo experiments demonstrated that treatment with PHI (50 mg/kg) in db/db mice effectively improved renal function and attenuated kidney injury by reducing the urinary albumin-to-creatinine ratio (UACR), mitigating podocyte apoptosis, and inhibiting inflammatory via modulation of the TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β signaling pathways.</p><p><strong>Conclusion: </strong>PHI inhibits inflammation and apoptosis in vitro and alleviates diabetic kidney injury in db/db mice by interfering TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β signaling pathways. Thus, this study reveals for the first time that PHI is a potential novel therapeutic agent for DN.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156314"},"PeriodicalIF":6.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated gut microbiome and UHPLC-MS metabolomics to reveal the prevention mechanism of pidanjiangtang granules on IGT Rats.","authors":"Yu Xie, Zirong Li, Yue Fan, Xinyi Liu, Ran Yi, Yaoyao Gan, Zixuan Yang, Shangjian Liu","doi":"10.1016/j.phymed.2024.156201","DOIUrl":"10.1016/j.phymed.2024.156201","url":null,"abstract":"<p><strong>Introduction: </strong>Pidanjiangtang (PDJT) is a traditional Chinese medicine formula empirically used to treat impaired glucose tolerance (IGT) based on the \"Pidan\" theory from the classic ancient book Nei Jing. However, the mechanism of PDJT intervention for IGT remains to be studied.</p><p><strong>Objective: </strong>This study aims to explore the mechanism of PDJT granules intervention in IGT by integrating gut microbiome and UHPLC-MS untargeted metabolomics.</p><p><strong>Materials and methods: </strong>The IGT model was established in 6-week-old male Sprague-Dawley (SD) rats by feeding them a high-fat diet and using an STZ injection. The low, medium, and high doses of PDJT were used for six weeks. metformin (Glucophage) was used as the positive control drug. The efficacy of PDJT was evaluated using fasting blood glucose (FBG), blood glucose maximum (BGmax), blood lipid, and inflammatory factor levels. Finally, 16S rDNA gut microbiome sequencing with metabolomics analysis was used to explore the pharmacological mechanism of PDJT intervention in IGT.</p><p><strong>Results: </strong>PDJT could reverse the phenotype of IGT rats, reduce blood glucose levels, improve lipid metabolism disorder, and reduce inflammatory response. Gut microbiome analysis found that PDJT can improve gut microbiota composition and abundance of three phyla (Firmicutes, Bacteroidota, Desulfobacterota) and four genera (unclassified_f__Lachnospiraceae, Ruminococcus, Allobaculum, Desulfovibrio), which play an important role in the process of PDJT intervention on glucose metabolism and lipid metabolism in IGT rats. UHPLC-MS untargeted metabolomics showed that PDJT could regulate the levels of 258 metabolites in lipid metabolism pathways, inflammatory response pathways, fat and protein digestion, and absorption. The combined analysis of the two omics showed that improving the body's metabolism by gut microbes may be the possible mechanism of PDJT in treating IGT. Thus, this study provides a new method to integrate gut microbiome and UHPLC-MS untargeted metabolomics to evaluate the pharmacodynamics and mechanism of PDJT intervention in IGT, providing valuable ideas and insights for future research on the treatment of IGT with traditional Chinese medicine.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156201"},"PeriodicalIF":6.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broussoflavonol F exhibited anti-proliferative and anti-angiogenesis effects in colon cancer via modulation of the HER2-RAS-MEK-ERK pathway.","authors":"Yiying Zhu, Xiaoli Li, Grace Gar-Lee Yue, Julia Kin-Ming Lee, Si Gao, Mengru Wang, Chun Kwok Wong, Wei-Lie Xiao, Clara Bik-San Lau","doi":"10.1016/j.phymed.2024.156243","DOIUrl":"10.1016/j.phymed.2024.156243","url":null,"abstract":"<p><strong>Background: </strong>A prenylated flavonoid, broussoflavonol F (BFF), was isolated from Macaranga genus with cytotoxicities against various cancer cells, though its underlying mechanisms have not been fully elucidated.</p><p><strong>Hypothesis: </strong>This study aimed to investigate the anti-tumor and anti-angiogenesis activities of BFF and its underlying mechanisms in colon cancer.</p><p><strong>Method: </strong>In the in vitro study, the cytotoxic effects of BFF in human colon cancer HCT-116 and LoVo cells were examined using MTT assay, BrdU assay and colony formation assay. The anti-proliferative effects of BFF in these cells were assessed via cell apoptosis and cell cycle analysis using flow cytometry. The anti-angiogenesis effects of BFF in human endothelial HEMC-1 cells were also detected using scratch wound healing assay and tube formation assay. While the in vivo effects of BFF in colon cancer were further examined in zebrafish embryos and HCT116 tumor-bearing mice. The underlying mechanisms of BFF were predicted using network pharmacology analysis, and Western blotting was performed to validate both in vitro and in vivo results.</p><p><strong>Results: </strong>BFF exhibited cytotoxicities on 5 colon cancer cell lines, as well as anti-proliferative activities via inducing apoptosis and cell cycle arrest at the G0/G1 phase in HCT116 and LoVo cells. BFF at 1.25-5 µM also suppressed cell proliferation in these two colon cancer cell lines by downregulating HER2, RAS, p-BRAF, p-MEK and p-Erk protein expressions. In addition, BFF at 2.5-5 µM could significantly decrease the length of subintestinal vessels of zebrafish embryos through decreasing mRNA expressions of NRP1a, PDGFba, PDGFRb, KDR, FLT1 and VEGRaa. Besides, BFF exhibited anti-angiogenesis activity via inhibiting cell proliferation, motility and tube formation in HMEC-1 cells. Furthermore, intraperitoneal administration of BFF (10 mg/kg) suppressed tumor growth and decreased the expression of tumor proliferation marker Ki-67 and angiogenesis marker CD31 in the tumor tissues in HCT116 tumor-bearing mice. BFF treatment could also significantly decrease expressions of RAS, p-BRAF, p-MEK and p-Erk in the tumor section, which are consistent with the in vitro results.</p><p><strong>Conclusions: </strong>This study revealed the anti-tumor and anti-angiogenesis effects of BFF in colon cancer. This is the first report of the in vitro and in vivo anti-proliferative activity of BFF in colon cancer through regulating the HER2-RAS-MEK-ERK pathway. These findings further support the research development of BFF as an anti-cancer agent in colon cancer.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156243"},"PeriodicalIF":6.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"20(R)-ginsenoside Rg3 alleviates diabetic retinal injury in T2DM mice by attenuating ROS-mediated ER stress through the activation of the Nrf2/HO-1 axis.","authors":"Wen-Lin Li, Ke Li, Wen-Guang Chang, Hui Shi, Wen-Xuan Zhang, Zi Wang, Wei Li","doi":"10.1016/j.phymed.2024.156202","DOIUrl":"10.1016/j.phymed.2024.156202","url":null,"abstract":"<p><strong>Background: </strong>Although our previous work confirmed 20(R)-ginsenoside Rg3 (R-Rg3), which is an active ingredient in the Panax Ginseng C.A. Meyer, to have good anti-diabetic activity, its beneficial effect on diabetic retinal injury was found to be limited.</p><p><strong>Purpose: </strong>This study aims to investigate the protective effects of R-Rg3 on diabetes-induced retinal injury and the associated molecular mechanisms of action.</p><p><strong>Methods: </strong>Diabetic retinal injury was induced in mice using a combination of a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). R-Rg3 (10 and 20 mg/kg) was subsequently administered for 6 weeks. The human retinal endothelial cells (HRECs) were subjected to high glucose (HG)-induced injury for the in vitro analysis and treated with R-Rg3 (4, 8, 16 μM), antioxidant N-Acetylcysteine (NAC, 1 mM) and Nrf2 inhibitor ML385 (5 μM). The mice retinas then underwent functional and histopathological analysis. Expression levels of proteins related to the Nrf2/HO-1 axis, tight junction proteins, endoplasmic reticulum (ER) stress and the apoptosis in retinal tissue and HRECs were determined by western blot. Expressions of ZO-1 and Nrf2 in the retina and HRECs were assessed by immunofluorescence. Additional evaluations included measuring body weights, fasting blood glucose (FBG), lipid levels and oxidative markers.</p><p><strong>Results: </strong>The results showed 6 weeks of R-Rg3 treatment significantly restored the functional changes and redox system imbalance that was induced by HFD/STZ in mice. R-Rg3 was also found to significantly reduce retinal barrier damage and thickness changes resulting from hyperglycaemia exposure. At the same time, R-Rg3 also protected HRECs from HG-induced damage. R-Rg3 could also activate Nrf2/HO-1 axis and inhibit endoplasmic reticulum stress as a means of alleviating retinal endothelial cells apoptosis. The molecular docking results also demonstrated that R-Rg3 had a good binding ability with Nrf2.</p><p><strong>Conclusion: </strong>Our study suggested Nrf2/HO-1 axis might be crucial for the ability of R-Rg3 to prevent diabetic retinal injury.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156202"},"PeriodicalIF":6.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}