Phytomedicine最新文献

{"title":"Key role of PPAR-γ-mediated suppression of the NFκB signaling pathway in rutin's antidepressant effect","authors":"","doi":"10.1016/j.phymed.2024.156178","DOIUrl":"10.1016/j.phymed.2024.156178","url":null,"abstract":"<div><h3>Background</h3><div>Depression is a chronic and recurrent disorder with an unknown etiology. Efficacious antidepressant treatments with minimal side effects are urgently needed. Neuroinflammation may contribute to depression, as anti-inflammatory drugs have been shown to alleviate depressive symptoms in clinical practice. Rutin, a naturally occurring flavonoid derived from plants, is abundant in many antidepressant herbs, including <em>Hemerocallis citrina Baroni</em>. Historical Chinese medical texts, including the renowned <em>Compendium of Materia Medica</em>, document <em>H. citrina Baroni</em> as possessing antidepressant properties. Rutin, one of its primary active constituents, is recognized for its anti-inflammatory effects. Despite this, little is known about its specific target and mechanism.</div></div><div><h3>Methods</h3><div>In the present study, molecular docking, and surface plasmon resonance imaging (SPRi) analysis were used to identify the special targets of rutin. Meanwhile, the potential antidepressant effects were evaluated in the chronic social defeat stress (CSDS) paradigm, an animal model of depression. Then, Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), Co-immunoprecipitation (Co-IP) as well as antagonists of PPAR-γ were utilized to investigate the mechanism underlying the antidepressant effect of rutin.</div></div><div><h3>Results</h3><div>Both molecular docking and SPRi analysis showed high docking scores and interactions between rutin and PPAR-γ. In vivo, rutin promoted the nuclear translocation of PPAR-γ in the hippocampus of mice, inhibited NFκB-mediated inflammatory pathways, and subsequently reduced the expression of pro-inflammatory factors (e.g., iNOS, IL-6), aligning with an antidepressant effect. However, this therapeutic effect was attenuated by GW9662, a specific antagonist of PPAR-γ.</div></div><div><h3>Conclusion</h3><div>As a result of activating PPAR-γ and inhibiting NFκB pathway activation, rutin reduces neuroinflammation and exhibits an antidepressant effect. These findings shed light on the antidepressant mechanism of rutin and could be valuable for the development of new antidepressants.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522728","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":"Benzoylmesaconine mitigates NLRP3 inflammasome-related diseases by reducing intracellular K⁺ efflux and disrupting NLRP3 inflammasome assembly.","authors":"Zhongyun Zhang, Chen Wu, Zilu Bao, Zhaoxiang Ren, Min Zou, Shuhui Lei, Kaiqun Liu, Xukun Deng, Shijin Yin, Zhaohua Shi, Liqin Zhang, Zhou Lan, Lvyi Chen","doi":"10.1016/j.phymed.2024.156154","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156154","url":null,"abstract":"<p><strong>Background: </strong>Benzoylmesaconine (BMA), a major alkaloid derived from the traditional Chinese medicine Aconitum carmichaeli Debx, exhibits potent anti-inflammatory properties. However, the precise mechanism underlying its action remains unclear.</p><p><strong>Purpose: </strong>This study aimed to investigate the inhibitory mechanism of BMA on the NLRP3 inflammasome and assess its therapeutic efficacy in NLRP3-related metabolic diseases.</p><p><strong>Methods: </strong>A classic NLRP3 inflammasome-activated bone marrow-derived macrophage (BMDM) model was established to evaluate BMA's effects on NLRP3 upstream and downstream protein expression, as well as pyroptosis. Two distinct animal disease models, MSU-induced gouty arthritis and DSS-induced colitis, were utilized to validate BMA's anti-inflammatory activity in vivo.</p><p><strong>Results: </strong>In vitro findings revealed that BMA can suppress NLRP3 inflammasome activation by inhibiting interleukin-1β (IL-1β) secretion and GSDMD-N protein expression. This mechanism involved blocking intracellular K⁺ efflux and interfering with the formation of NLRP3 inflammasomes. In vivo studies demonstrated that BMA significantly alleviated inflammatory symptoms in MSU-induced acute gout and DSS-induced colitis models.</p><p><strong>Conclusion: </strong>These findings suggest that BMA effectively inhibits the activation of the NLRP3 signaling pathway through dual mechanisms: reducing intracellular K⁺ efflux and disrupting NLRP3 inflammasome assembly. This multifaceted action highlights the therapeutic potential of BMA for NLRP3-related diseases.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506461","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":"Anti-inflammatory oligosaccharide licensed mesenchymal stem cells allow prolonged survival of septic rats via the promotion of glutathione synthesis.","authors":"Qingtong Yu, Linzhi Zhang, Zhe Wang, Qilong Wang, Xuan Sun, Wenwen Deng, Xia Cao, Jiangnan Yu, Ximing Xu","doi":"10.1016/j.phymed.2024.156173","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156173","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) possess the capability to mitigate multiorgan failure (MOF) and reduce mortality rates in sepsis. However, their survival is significantly limited due to oxidative stress responses triggered by excessive sepsis inflammation. Previous studies have demonstrated that the paracrine effect of MSCs can be enhanced by cytokine stimuli such as IL-1β, TNF-α, and IFN-γ, a process known as inflammatory licensing. This enhancement, however, may potentially lead to the apoptosis of MSCs.</p><p><strong>Purpose: </strong>To investigate the therapeutic effects of Fructus Lycii oligosaccharide (FLO)-nasal mucosa-derived ectodermal MSCs (EMSCs) on septic rats and the underlying mechanisms.</p><p><strong>Study design and methods: </strong>FLO was screened from 21 distinct saccharides derived from traditional Chinese medicine (TCM), utilizing macrophage lipid raft chromatography prepared by our laboratory as the primary screening method.. The comparison of EMSCs primed with/without FLO was assessed through RNA-seq. Cecal ligation and puncture (CLP) surgery was performed in the CLP, EMSCs, and FLO-EMSCs groups (n = 10). The NC group underwent cecal ligation without puncture. The therapeutic effects of EMSCs and FLO-EMSCs on septic rats were evaluated through multiple tests including RT-PCR, western blot, histochemical staining, etc. RESULTS: FLO promoted M2 polarization of macrophages and enhanced the paracrine effect of EMSCs, without inducing apoptosis. Furthermore, FLO promoted GSH synthesis in EMSCs, aiding in the removal of reactive oxygen species (ROS) within these cells. The FLO-treated EMSCs demonstrated enhanced protection against pyroptosis in macrophages, thereby preventing immune paralysis during sepsis.</p><p><strong>Conclusion: </strong>This study presents an innovative approach for enhancing the anti-inflammatory properties of MSCs using a TCM-derived oligosaccharide, thereby improving their therapeutic efficacy in sepsis models.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546876","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":"Ganjiang Huangqin Huanglian Renshen Decoction protects against ulcerative colitis by modulating inflammation, oxidative stress, and gut microbiota","authors":"","doi":"10.1016/j.phymed.2024.156172","DOIUrl":"10.1016/j.phymed.2024.156172","url":null,"abstract":"<div><h3>Background</h3><div>Ulcerative colitis (UC) is a disease that is difficult to treat and has been associated with high rates of recurrence. Moreover, the current medications for UC induce serious side effects following prolonged use. Ganjiang Huangqin Huanglian Renshen Decoction (GJHQHLRSD), has been traditionally used to treat UC. However, its protective mechanisms have not been fully studied.</div></div><div><h3>Purpose</h3><div>In this study the mechanisms by which GJHQHLRSD treats UC was investigated.</div></div><div><h3>Methods</h3><div>The GJHQHLRSD and GJHQHLRSD drug-containing serum (GJHQHLRSD-DS) were characterized using LC-MS/MS. The therapeutic effect of GJHQHLRSD on dextran sodium sulfate (DSS)-induced UC was explored by assessing various parameters including intestinal flora 16S rRNA, intestinal barrier function, oxidative stress (OS) response, inflammatory cytokines, colonic histopathological injury, colon length, disease activity index (DAI) and body weight.</div></div><div><h3>Results</h3><div>Treatment with GJHQHLRSD increased body weight, ameliorated colon length shortening and edema, reduced the DAI score, improved the pathological injury, down-regulated the levels of IL-1β, IL-6, IL-8, TNF-α, LPS, LDH, TLR4, and NLRP3, and up-regulated the ZO-1 and Occludin levels in UC mice. It also decreased intestinal oxidative stress in UC mice and improved mitogenic activity by modulating mitochondrial ultrastructure as well as the expression level of PINK1, LC3-II/Ⅰ, Beclin-1, p62, and Parkin proteins. In addition, we found that the effects of GJHQHLRSD on UC mice were inhibited by 3-MA.GJHQHLRSD treatment reduced the imbalance of intestinal flora in UC mice, by regulating the inflammation and oxidative stress.</div></div><div><h3>Conclusion</h3><div>These findings suggested that GJHQHLRSD effectively attenuated inflammatory responses, inhibited the TLR4/NF-κB/NLRP3 signalling, oxidative stress, and modulated the gut microbiota, and alleviated the DSS-induced UC symptoms, making it a promising and innovative therapeutic option for the treatment of UC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xianglian pill alleviates ulcerative colitis by inhibiting M1 macrophage polarization via modulation of energy metabolite itaconate","authors":"","doi":"10.1016/j.phymed.2024.156179","DOIUrl":"10.1016/j.phymed.2024.156179","url":null,"abstract":"<div><h3>Background</h3><div>Xianglian pill (XLP) is a traditional Chinese medicine (TCM) that is widely used to treat ulcerative colitis (UC). However, its mechanism of action in UC is unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the mechanism of action of XLP in treating UC and role of M1 macrophage polarization in this process.</div></div><div><h3>Study design</h3><div>In vivo experiments were performed using UC mice while in vitro experiments were conducted using RAW264.7 cells.</div></div><div><h3>Methods</h3><div>Mice were administered 3 % dextran sulfate to induce UC model and then treated with XLP. Changes in histopathology and pro-inflammatory cytokines were evaluated. The levels of M1 macrophages in mesenteric lymph nodes were detected by flow cytometry. Colon metabolite levels were analyzed using an energy metabolomic assay. To assess itaconate's impact, both in vivo (mice) and in vitro (RAW264.7 cells) models were employed. Immunofluorescence staining was used to measure the expression levels of TNF-α, IL-6, and iNOS, while qRT-PCR was utilized to quantify the mRNA levels of TET2, STAT1, and Nfkbiz.</div></div><div><h3>Results</h3><div>XLP alleviated ulcerative damage and reduced TNF-α and IL-6 levels in colon, and also downregulated the levels of M1 macrophages and modulated the state of energy metabolism. Specifically, XLP significantly increased ITA level in colonic tissue and this increase was significantly associated with decreased levels of M1 macrophages and alleviation of UC following XLP treatment. Moreover, ITA directly suppressed the polarization of macrophage from M0 to M1 phenotype, accompanied by the decrease of TNF-α, IL-6, and iNOS levels. Further, ITA decreased inflammatory responses in M1 macrophage by inhibiting the TET2/STAT1 and TET2/NF-κB signaling pathways.</div></div><div><h3>Conclusion</h3><div>XLP can treat UC by suppressing M1 macrophage polarization via increasing the level of energy metabolite ITA.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522729","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":"Acacetin alleviates rheumatoid arthritis by targeting HSP90 ATPase domain to promote COX-2 degradation.","authors":"Wenshuang Wang, Shanshan Zhai, Wen Yang, He Gao, Nianwei Chang, Man Zhang, Yuanyuan Hou, Gang Bai","doi":"10.1016/j.phymed.2024.156171","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156171","url":null,"abstract":"<p><strong>Background: </strong>Inflammation plays a significant role in initiating and sustaining rheumatoid arthritis (RA). Acacetin, a natural flavonoid compound, exhibits excellent anti-inflammatory effects specifically for RA. However, its relevant targets and molecular mechanisms remain to be elucidated.</p><p><strong>Purpose: </strong>This study aims to investigate the mechanism of acacetin in the therapeutic efficacy of acacetin in RA and search for new therapeutic options for RA treatment.</p><p><strong>Methods: </strong>A collagen-induced RA mouse model was established to evaluate the therapeutic effect of acacetin. Acacetin functional probes were synthesized to capture potential target proteins in RAW264.7 cells. Various small molecule-protein interaction methods were conducted to verify the binding of acacetin to target protein. Molecular docking and site directed mutagenesis tests were performed to analyze the specific binding sites. Co-immunoprecipitation, immunofluorescence assay and western blot were engineered to explore the effect of acacetin on COX-2 degradation by targeting HSP90.</p><p><strong>Results: </strong>Acacetin specifically binds to the ATP domain of HSP90, to facilitate the dissociation between HSP90 and COX-2, inducing the ubiquitin-degradation of COX-2 in macrophages. Acacetin suppressed the production of pro-inflammatory cytokines, as well as inflammatory related pathways, exerting excellent anti-inflammatory effects in RA.</p><p><strong>Conclusions: </strong>This research proved that acacetin, a novel HSP90 ATPase inhibitor, inhibits the functional folding of the client protein COX-2, promoting its ubiquitin degradation for anti-inflammation. Targeting HSP90 is a viable strategy to inhibit inflammation, affording a distinct way to managing joint inflammation and pains associated with RA.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569423","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":"Astragaloside IV and cycloastragenol promote liver regeneration through regulation of hepatic oxidative homeostasis and glucose/lipid metabolism","authors":"","doi":"10.1016/j.phymed.2024.156165","DOIUrl":"10.1016/j.phymed.2024.156165","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The regenerative capacity of the liver is pivotal for mitigating various forms of liver injury and requires the rapid proliferation of hepatocytes. Aquaporin-9 (AQP9) provides vital support for hepatocyte proliferation by preserving hydrogen peroxide (H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;) oxidative balance and glucose/lipid metabolism equilibrium within hepatocytes. Our previous study demonstrated that Radix Astragali (RA) decoction promotes liver regeneration by upregulating hepatic expression of AQP9, possibly via two major active constituents: astragaloside IV (AS-IV) and cycloastragenol (CAG).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To verify that upregulated AQP9 expression in hepatocytes maintains liver oxidative balance and glucose/lipid metabolism homeostasis, and is the main pharmacological mechanism by which AS-IV and CAG promote liver regeneration.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study Design/Methods&lt;/h3&gt;&lt;div&gt;Effects of AS-IV and CAG on liver regeneration were scrutinized using a mouse model of 70 % partial hepatectomy (PHx). AQP9-targeted liver regeneration mediated by AS-IV and CAG was verified using AQP9 gene knockout mice (AQP9&lt;sup&gt;−/−&lt;/sup&gt;). The AQP9 protein expression pattern in hepatocytes was determined using tdTomato-tagged AQP9 transgenic mice (AQP9-RFP). Potential mechanisms of AS-IV and CAG on liver regeneration were studied using real-time quantitative PCR, immunoblotting, staining with hematoxylin and eosin, oil red O, and periodic acid-Schiff, and immunofluorescence, immunohistochemistry, HyPerRed fluorescence, and biochemical analyses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;AS-IV and CAG promoted substantial liver regeneration and increased hepatic AQP9 expression in wild-type mice (AQP9&lt;sup&gt;+/+&lt;/sup&gt;) following 70 % PHx, but had no discernible benefits in AQP9&lt;sup&gt;−/-&lt;/sup&gt; mice. Both saponin compounds also helped maintain oxidative homeostasis by reducing levels of oxidative stress markers (reactive oxygen species [ROS], H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;, and malondialdehyde) and elevating levels of ROS scavengers (glutathione and superoxide dismutase) in AQP9&lt;sup&gt;+/+&lt;/sup&gt; mice post-70 % PHx. This further activated the PI3K-AKT and insulin signaling pathways, thereby fostering liver regeneration. Furthermore, AS-IV and CAG both promoted hepatocyte glycerol uptake, increased gluconeogenesis, facilitated lipolysis, reduced glycolysis, and inhibited glycogen deposition, thus ensuring the energy supply required for liver regeneration.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This research is the first to demonstrate AS-IV and CAG as major active ingredients of RA that promote liver regeneration by upregulating hepatocyte AQP9 expression, improving hepatocyte glucose/lipid metabolism, and reducing oxidative stress damage, constituting a crucial pharmacological mechanism underlying the liver-protective effects of RA. The augmentation of hepatocyte AQP9 expression underscores an important aspect of the Qi-tonifying effect of RA.","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506460","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":"The volatile oil of Acorus tatarinowii Schott ameliorates Alzheimer's disease through improving insulin resistance via activating the PI3K/AKT pathway","authors":"","doi":"10.1016/j.phymed.2024.156168","DOIUrl":"10.1016/j.phymed.2024.156168","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Alzheimer's disease (AD) presently stands as the most prevalent neurodegenerative disease. Existing research underscores the pivotal role of insulin signaling in the progression of AD. &lt;em&gt;Acorus tatarinowii Schott&lt;/em&gt; (SCP), a traditional Chinese herbal, is employed for AD treatment in China. The volatile oil of &lt;em&gt;Acorus tatarinowii Schott&lt;/em&gt; (SCP-oil) is the active component. However, its impact on AD-associated insulin resistance (AD-IR) remains inadequately investigated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study used network pharmacology and experimental to investigate the effects and mechanisms of SCP-oil on cognitive improvement in AD by inhibiting IR.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;GC-Q/TOF-MS was employed to analyze the chemical composition of SCP-oil, while network pharmacology predicted the targets associated with SCP-oil in treating AD-IR to identify its regulatory mechanism. IR in the brain was simulated by intracerebroventricular streptozotocin administration (ICV-STZ). The neuroprotective and cognitive improvement effects of SCP-oil were assessed using the Morris water maze and hematoxylin and eosin, as well as Nissl staining. The expression levels of Neun and proteins related to p-tau, tau, amyloid-beta (Aβ), apoptosis, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were measured using immunohistochemistry and Western blotting, respectively. Dexamethasone (DXM)-induced HT22 cells were used for IR modeling. Chemical analysis determined the glucose consumption rate, and periodic acid Schiff staining was employed to detect glycogen deposition. Western Blots were utilized to investigate the expression of characteristic AD proteins, apoptosis-related proteins, and PI3K/AKT pathway-related proteins. The apoptosis rate was detected by flow cytometry. Reverse validation was further performed using LY294002 to evaluate the pharmacodynamic effects of SCP-oil after PI3K/AKT pathway inhibition.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 25 chemical constituents were identified in SCP-oil. The network pharmacology findings indicated that SCP-oil holds the potential to ameliorate IR in the brain by activating the PI3K/AKT pathway, thereby improving AD. SCP-oil significantly improved ICV-STZ-induced cognitive dysfunction and pathological damage, reduced neuronal loss, Aβ deposition, and tau protein hyperphosphorylation, inhibited cell apoptosis, and activated the PI3K/AKT signaling pathway. Neuron loss, Aβ deposition, and tau protein hyperphosphorylation and cell apoptosis were further enhanced following treatment with LY294002, while the PI3K/AKT signaling pathway was further inhibited, and the protective effect of SCP-oil was weakened.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;SCP-oil exhibited the potential to ameliorate brain IR, inhibiting cell apoptosis by activating the PI3K/AKT signaling pathway, thereby improving learning and memory ability.&lt;/div&gt;&lt;/","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564653","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":"4-Hydroxydictyolactone alleviates cerebral ischemia injury by regulating neuroinflammation and autophagy via AMPK signaling pathway","authors":"","doi":"10.1016/j.phymed.2024.156157","DOIUrl":"10.1016/j.phymed.2024.156157","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral ischemia (CI), a cerebrovascular disorder, is a major contributor to disability and mortality. Marine-derived compounds are an important source of new neuroprotective drug candidates. Xenicane-type diterpenes from brown algae of the genus <em>Dictyota</em> have exhibited potential neuroprotective effects against CI injury, attributed to their antioxidant properties. However, whether there are other underlying neuroprotective mechanisms of xenicane diterpenes against CI is still ambiguous.</div></div><div><h3>Purpose</h3><div>This study aims to elucidate the neuroprotective efficacy and mechanism of 4-hydroxydictyolactone (HDTL) in the treatment of CI.</div></div><div><h3>Methods</h3><div>The LPS-induced BV2 cell model was used for anti-neuroinflammatory activity assay. Tandem Mass Tag (TMT)-based quantitative proteomics was employed to identify underlying mechanisms. The OGD/R-induced SH-SY5Y cell model and a MCAO mice model were used to assess the neuroprotective effect of HDTL against CI in vitro and in vivo.</div></div><div><h3>Results</h3><div>HDTL reduced inflammation in LPS-stimulated BV2 cells by inhibiting the IKK/IκB/NF-κB pathway and by enhancing AMPK phosphorylation. Additionally, in SH-SY5Y cells treated with OGD/R, HDTL facilitated autophagy and reduced apoptosis. The neuroprotective properties of HDTL were abrogated in AMPK- silenced SH-SY5Y cells. In MCAO mice, HDTL ameliorated CI injury as evidenced by decreases in neurological deficit scores and cerebral infarction. HDTL also promoted autophagy and reduced apoptosis in vivo through both the AMPK/mTOR and IKK/IκB/NF-κB pathways.</div></div><div><h3>Conclusion</h3><div>HDTL exhibits neuroprotective effects through regulating the AMPK/mTOR and IKK/IκB/NF-κB pathways. These findings suggest that HDTL is a promising therapeutic candidate for CI treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472879","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":"Tong-Qiao-Huo-Xue Decoction promotes synaptic remodeling via cAMP/PKA/CREB pathway in vascular dementia rats","authors":"","doi":"10.1016/j.phymed.2024.156166","DOIUrl":"10.1016/j.phymed.2024.156166","url":null,"abstract":"<div><h3>Background</h3><div>Tong-Qiao-Huo-Xue Decoction (TQHXD) is a traditional Chinese medicinal formula widely used in the treatment of vascular dementia (VD). Although it has demonstrated good clinical efficacy, the specific molecular mechanisms underlying its therapeutic effects on VD remain unclear.</div></div><div><h3>Objective</h3><div>This study aimed to elucidate the neuroprotective mechanisms of TQHXD to provide a scientific basis for the clinical treatment of VD.</div></div><div><h3>Methods</h3><div>The chemical components of TQHXD were qualitatively analyzed using ultra-performance liquid chromatography (UPLC) and gas chromatography (GC). Network pharmacology predicted the potential protective mechanisms of TQHXD against VD. A rat model of VD was established through bilateral vessel occlusion (2-VO), and an oxygen-glucose deprivation/reperfusion (OGD/R) model was used to induce damage to neuronal cells of the hippocampus. <em>In vivo</em> experiments assessed changes in cerebral blood flow, learning and memory capabilities, hippocampal neuronal morphology, dendritic length, dendritic spine density, and synapse number in rats. We examined the expression of synaptic remodeling-related proteins and pathway proteins in the hippocampal region. <em>In vitro</em> assays evaluated cell viability, apoptosis, reactive oxygen species (ROS) levels, and expression of synaptic remodeling-related proteins and signaling pathway.</div></div><div><h3>Results</h3><div>Multiple active components were identified in TQHXD. KEGG enrichment analysis suggested that the therapeutic effects of TQHXD on VD may be related to the cAMP signaling pathway. Treatment with TQHXD significantly improved learning and memory performance in VD rats, improved hippocampus morphology, and increased dendritic length, dendritic spine density, and number of synapses. Furthermore, TQHXD improved cell viability, reduced apoptosis, and decreased intracellular ROS levels <em>in vitro</em>. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assay results collectively demonstrated that TQHXD upregulated the expression of synaptic remodeling-related proteins and pathway-related proteins both <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Conclusions</h3><div>TQHXD treated VD by promoting synaptic remodeling in hippocampal neurons, likely through activation of the cAMP/PKA/CREB pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}