Phytomedicine最新文献

{"title":"SQYC formula improves the efficacy of PD-1 monoclonal antibodies in MSS colorectal cancer by regulating dendritic cell mitophagy via the PINK1-Parkin pathway","authors":"Hong Wang ,&nbsp;Yi Ji ,&nbsp;Shan Deng ,&nbsp;Xiao ying Qin ,&nbsp;Xie tao Ye ,&nbsp;Ye yang Sun ,&nbsp;Xiao yu Che ,&nbsp;Lin Yang ,&nbsp;Chu yue Huang ,&nbsp;Yan Chen ,&nbsp;Yu ping Liu","doi":"10.1016/j.phymed.2025.156388","DOIUrl":"10.1016/j.phymed.2025.156388","url":null,"abstract":"<div><h3>Background</h3><div>Microsatellite stable (MSS) colorectal carcinomas (CRCs) exhibit poor responsiveness to immunotherapy such as immune checkpoint inhibitors (ICIs). In the realm of clinical cancer treatment, traditional Chinese medicines (TCMs) are extensively utilized for their immunomodulatory properties. Shen Qi Yi Chang (SQYC), a clinical prescription for CRC treatment, improve the life quality of CRC patients and enhance their immune function.</div></div><div><h3>Purpose</h3><div>This study was to reveal the effect and mechanism of SQYC in improving the effect of PD-1 inhibitors in the treatment of MSS-type CRC.</div></div><div><h3>Methods</h3><div>CT26-luc <em>in situ</em> CRC tumor model and human CRC organoid model was established to evaluate the anti-tumor efficacy of SQYC combined with PD-1 inhibitor. Flow cytometry analysis was utilized to investigate the effect of SQYC on the infiltration and immune function of TILs and DCs in the immune microenvironment. Following this, RNA sequencing analysis, seahorse, TEM and immunofluorescence were performed to regulation of SQYC on mitophagy in DCs cells. UPLC-Q-TOF/MS and molecular docking were used to reveal the key blood-entering components of SQYC-regulated PINK1-parkin pathway.</div></div><div><h3>Results</h3><div>The SQYC-containing serum improved the efficacy of sintilimab in MSS CRC organoid model. After combined administration of 11.4 g/kg/day SQYC extract and 5 mg/kg α-PD-1, it was observed that SQYC enhanced the efficacy of PD-1 inhibitor against MSS CRC. Flow cytometry and immunofluorescence analysis revealed an augmented infiltration of tumor-infiltrating lymphocytes (TILs) and an improved antigen presentation function of dendritic cells (DCs). Notably, RNA sequencing analysis demonstrated an evident correlation with mitochondrial function related pathways following SQYC treatment. Mechanistically, SQYC promoted mitophagy in DCs via the PINK1-Parkin pathway, thereby improving mitochondrial quality, energy metabolism, and mitochondrial dynamics. Evaluation of the blood components of SQYC coupled with molecular docking, demonstrated good binding affinity with PINK1/PARKIN/LC3.</div></div><div><h3>Conclusion</h3><div>Our findings highlight SQYC as a promising candidate for improving immunotherapy in MSS CRC, suggesting that targeting PINK1-Parkin in DCs could represent a novel strategy for improving the efficacy of ICIs. Furthermore, it provides new theoretical and scientific underpinnings to enhance the clinical efficacy of immunosuppressants.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156388"},"PeriodicalIF":6.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010332","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":"Harnessing natural saponins: Advancements in mitochondrial dysfunction and therapeutic applications","authors":"Hongmei Liu ,&nbsp;Huan Wang ,&nbsp;Xinyu Lin ,&nbsp;Min Xu ,&nbsp;Wenying Lan ,&nbsp;Jinlian Wang","doi":"10.1016/j.phymed.2025.156383","DOIUrl":"10.1016/j.phymed.2025.156383","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial dysfunction plays a crucial role in the development of a variety of diseases, notably neurodegenerative disorders, cardiovascular diseases, metabolic syndrome, and cancer. Natural saponins, which are intricate glycosides characterized by steroidal or triterpenoid structures, have attracted interest due to their diverse pharmacological benefits, including anti-inflammatory, antiviral, and anti-aging effects.</div></div><div><h3>Purpose</h3><div>This review synthesizes recent advancements in understanding mitochondrial dysfunction and explores how saponins can modulate mitochondrial function. It focuses on their potential applications in neuroprotection, cardiovascular health, and oncology.</div></div><div><h3>Study design</h3><div>The review incorporates a comprehensive literature analysis, highlighting the interplay between saponins and mitochondrial signaling pathways. Specific attention is given to the effects of saponins like ginsenoside Rg2 and 20(S)-protopanaxatriol on mitophagy and their neuroprotective, anti-aging, and synergistic therapeutic effects when combined.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive review of current research and clinical trials using PubMed, Google Scholar, and SciFinder databases. The search focused on saponins' role in mitochondrial function and their therapeutic effects, including \"saponins\", \"mitochondria\" and \"mitochondrial function\". The analysis primarily focused on articles published between 2011 and 2024.</div></div><div><h3>Results</h3><div>The findings indicate that certain saponins can enhance mitophagy and modulate mitochondrial signaling pathways, showing promise in neuroprotection and anti-aging. Additionally, combinations of saponins have demonstrated synergistic effects in myocardial protection and cancer therapy, potentially improving therapeutic outcomes.</div></div><div><h3>Conclusion</h3><div>Although saponins exhibit significant potential in modulating mitochondrial functions and developing innovative therapeutic strategies, their clinical applications are constrained by low bioavailability. Rigorous clinical trials are essential to translate these findings into effective clinical therapies, ultimately improving patient outcomes through a deeper understanding of saponins’ impact on mitochondrial function.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156383"},"PeriodicalIF":6.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029334","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":"Redox imbalance driven epigenetic reprogramming and cardiovascular dysfunctions: phytocompounds for prospective epidrugs","authors":"Subham Saraswata Jyotirmaya ,&nbsp;Suvasmita Rath ,&nbsp;Jagneshwar Dandapat","doi":"10.1016/j.phymed.2025.156380","DOIUrl":"10.1016/j.phymed.2025.156380","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Cardiovascular diseases (CVDs) are the major contributor to global mortality and are gaining incremental attention following the COVID-19 outbreak. Epigenetic events such as DNA methylation, histone modifications, and non-coding RNAs have a significant impact on the incidence and onset of CVDs. Altered redox status is one of the major causative factors that regulate epigenetic pathways linked to CVDs. Various bioactive phytocompounds used in alternative therapies including Traditional Chinese Medicines (TCM) regulate redox balance and epigenetic phenomena linked to CVDs. Phytocompound-based medications are in the limelight for the development of cost-effective drugs with the least side effects, which will have immense therapeutic applications.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This review comprehends certain risk factors associated with CVDs and triggered by oxidative stress-driven epigenetic remodelling. Further, it critically evaluates the pharmacological efficacy of phytocompounds as inhibitors of HAT/HDAC and DNMTs as well as miRNAs regulator that lowers the incidence of CVDs, aiming for new candidates as prospective epidrugs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;PRISMA flow approach has been adopted for systematic literature review. Different Journals, computational databases, search engines such as Google Scholar, PubMed, Science Direct, Scopus, and ResearchGate were used to collect online information for literature survey. Statistical information collected from the World Health Organization (WHO) site (&lt;span&gt;&lt;span&gt;https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;) and the American Heart Association of Heart Disease and Stroke reported the international and national status of CVDs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The meta-analysis of various studies is elucidated in the literature, shedding light on major risk factors such as socioeconomic parameters, which contribute highly to redox imbalance, epigenetic modulations, and CVDs. Going forward, redox imbalance driven epigenetic regulations include changes in DNA methylation status, histone modifications and non-coding RNAs expression pattern which further regulates global as well as promoter modification of various transcription factors leading to the onset of CVDs. Further, the role of various bioactive compounds used in herbal medicine, including TCM for redox regulation and epigenetic modifications are discussed. Pharmacological safety doses and different phases of clinical trials of these phytocompounds are elaborated on, which shed light on the acceptance of these phytocompounds as prospective drugs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This review suggests a strong linkage between therapeutic and preventive measures against CVDs by targeting redox imbalance-driven epigenetic reprogramming using phytocompounds as prospective epidrugs. Future in-depth research is required to evaluat","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156380"},"PeriodicalIF":6.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010254","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":"Shouhui Tongbian Capsule ameliorates obesity by enhancing energy consumption and promoting lipolysis via cAMP-PKA pathway","authors":"Kaiyi Wu ,&nbsp;Jiangying Kuang ,&nbsp;Nana Huang ,&nbsp;Lisong Sheng ,&nbsp;Jianchao Li ,&nbsp;Rongrong Li ,&nbsp;Liping Gong ,&nbsp;Qinghua Lu ,&nbsp;Runping Liu ,&nbsp;Rong Sun","doi":"10.1016/j.phymed.2025.156375","DOIUrl":"10.1016/j.phymed.2025.156375","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of obesity and its associated diseases has sharply increased, becoming a global health issue. White adipose tissue (WAT), responsible for lipid storage via hyperplasia and hypertrophy, and brown adipose tissue (BAT), which facilitates energy dissipation, have increasingly been recognized as critical regulators of weight loss. Shouhui Tongbian Capsule (SHTB) has traditionally been used for detoxification, weight loss, and lipid reduction, and clinical evidence supports its use for relieving constipation. In traditional Chinese medicine (TCM), \"dissipating turbidity\" is seen as a shared approach to treating both constipation and obesity. Our evidence suggests that SHTB improves obesity and metabolic disorders, but the underlying mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to evaluate the pharmacological effects of SHTB on obesity and to explore the underlying mechanisms involved.</div></div><div><h3>Methods</h3><div>Obese mice induced by a high-fat diet were treated with SHTB, and effects on body weight, adipose tissue, and metabolism were assessed. Active ingredients were identified through UPLC-MS, while metabolomics and RNA sequencing were performed to explore the mechanisms of SHTB in obesity, and molecular biology techniques validated its effects on energy consumption and lipolysis in adipose tissue. Finally, rescue experiments <em>in vivo and in vitro</em> confirmed the proposed mechanisms.</div></div><div><h3>Results</h3><div>SHTB significantly reduced body weight, body fat percentage, and WAT mass while increasing BAT weight, and enhancing energy expenditure. Metabolomics and RNA sequencing indicated activation of the G-protein coupled receptor signaling and cAMP-PKA pathway, leading to increased lipolysis in WAT and enhanced thermogenesis in BAT. H89, a PKA agonist, counteracted these effects, supporting the involvement of cAMP-PKA signaling.</div></div><div><h3>Conclusion</h3><div>SHTB may prevent obesity by promoting lipolysis and enhancing BAT thermogenesis via the cAMP-PKA pathway, offering a potential therapeutic approach for obesity management.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156375"},"PeriodicalIF":6.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029348","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-colorectal cancer actions of Glycyrrhiza uralensis Fisch. and its underlying mechanism via HPLC integration and network pharmacological approaches","authors":"Hong Duan ,&nbsp;Wei Wang ,&nbsp;Ying Shi ,&nbsp;Li Wang ,&nbsp;Ghulam Jilany Khan ,&nbsp;Mengmeng Luo ,&nbsp;Jing Zhou ,&nbsp;Jianhua Yang ,&nbsp;Chenghui He ,&nbsp;Fei Li ,&nbsp;Henggui Hu ,&nbsp;Kefeng Zhai","doi":"10.1016/j.phymed.2025.156370","DOIUrl":"10.1016/j.phymed.2025.156370","url":null,"abstract":"<div><h3>Background</h3><div>The therapeutic and prognostic outcomes for colorectal cancer (CRC) remain unsatisfactory. Among multiple reported bioactive functionalities of <em>Glycyrrhiza uralensis</em> Fisch. one vital recently reported activity is its therapeutic role against numerous cancers but limited information is available related to its underlying key mechanisms and therapeutically active ingredients, especially against CRC treatment.</div></div><div><h3>Objective</h3><div>The aim of current study aims is to reconnoiter <em>G. uralensis</em> pharmacological basis and primary molecular mode of action in treating CRC.</div></div><div><h3>Methods</h3><div>For examining the <em>G. uralensis</em> active ingredients and underlying mechanism investigation against CRC including, potential anti-CRC phytochemicals, targets, and related signaling pathways, HPLC and Network-pharmacology analysis techniques was employed, respectively. Whereas, for binding capabilities of active components to their targets, molecular-docking, molecular dynamic simulation technique employed and cell proliferation assays screened the best anti-CRC components, followed by biological function experiments on SW480 cells for verification. Finally, the SW480-xenograft model and subsequent related experiments further confirmed the effect of Liquiritin on CRC.</div></div><div><h3>Results</h3><div>Seven compounds were identified from <em>G. uralensis</em> through HPLC. Network pharmacology and molecular docking results indicated that <em>G. uralensis</em> components exhibited significant anti-cancer effects. These effects were mediated through cancer and MAPK-related signaling pathways, targeting TP53, SRC, STAT3, and PIK3CA proteins. <em>In-vitro</em> experiments showed that liquiritin had better anti-CRC effects compared to other components as it significantly repressed the SW480 propagation, development of colony, relocation, and invasion. Additionally, liquiritin has been shown to significantly reduce tumor size in tumor-bearing mice by targeting p53 and inhibiting the p38 MAPK pathway.</div></div><div><h3>Conclusion</h3><div>In <em>G. uralensis</em>, main API is liquiritin that target CRC tumorigeneses via inhibition of p53 and p38 MAPK, thus can be used for CRC therapy. The findings provide a solid pharmacological basis and potential therapeutic targets for <em>G. uralensis</em> in the treatment of CRC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156370"},"PeriodicalIF":6.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010247","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 activity of essential oil from medicinal plants: An insight into molecular mechanism, in-silico studies and signaling pathways","authors":"Lopamudra Subudhi,&nbsp;Hrudayanath Thatoi,&nbsp;Amrita Banerjee","doi":"10.1016/j.phymed.2025.156364","DOIUrl":"10.1016/j.phymed.2025.156364","url":null,"abstract":"<div><h3>Background</h3><div>Medicinal plants have historically been the cornerstone of treatment for a myriad of ailments. With modern pharmacology, many contemporary drugs have been derived from traditional medicine practices. Essential oils from these plants, known for their anti-inflammatory capabilities, have played a significant role in treating conditions such as cardiovascular and inflammatory skin diseases, as well as joint inflammation. This study revisits these ancient remedies to further explore their efficacy and mechanisms in the modern context.</div></div><div><h3>Focus Area</h3><div>This review focuses on identifying and analysing the primary phytochemical in medicinal plants that exhibit anti-inflammatory properties. The chemical classes of interest include alkaloids, polyphenols, terpenoids, flavonoids, saponins, and tannins, which are prevalent in the essential oils derived from therapeutic plants. By understanding their role in modulating molecular pathways, this study aims to highlight their potential in the treatment of inflammatory diseases.</div></div><div><h3>Methods</h3><div>The study employs in silico techniques such as molecular modelling and docking to examine the pharmacokinetics and toxicity profiles of selected phytochemical. This approach facilitates a deeper understanding of how these natural compounds interact at the molecular level, either as activators or inhibitors, which can influence various biochemical pathways related to inflammation.</div></div><div><h3>Results</h3><div>Preliminary findings suggest that specific phytochemical significantly modulate inflammatory pathways, offering potential therapeutic targets. The analysis reveals that these natural substances can effectively reduce inflammation without the adverse side effects commonly associated with synthetic drugs. The study provides a detailed characterization of the active components within essential oils and their respective anti-inflammatory actions.</div></div><div><h3>Conclusion</h3><div>The review underscores the immense potential for medicinal plants as a source for developing new and safer pharmaceuticals aimed at treating inflammatory conditions. By harnessing the power of natural phytochemical, there is a promising avenue for creating innovative drug therapies. This study encourages further research into the utilization of natural plant products, promoting a broader application in medicinal treatments and a return to nature-centric solutions in healthcare.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156364"},"PeriodicalIF":6.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041147","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":"Yu-Xue-Bi capsule ameliorates aggressive synovitis and joint damage in rheumatoid arthritis via modulating the SUCNR1/HIF-1α/TRPV1 axis.","authors":"Wenjia Chen, Chu Zhang, Mingzhu Xu, Tao Li, Xin Li, Peihao Li, Xun Gong, Yang Qu, Chunling Zhou, Xia Mao, Na Lin, Wei Liu, Quan Jiang, Haiyu Xu, Yanqiong Zhang","doi":"10.1016/j.phymed.2024.156354","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156354","url":null,"abstract":"<p><strong>Background: </strong>Specific treatment for rheumatoid arthritis (RA) is still an unmet need. Yu-Xue-Bi (YXB) capsule effectively treats RA with blood stasis syndrome (BS). However, its mechanism remains unclear.</p><p><strong>Purpose: </strong>Exploring and elucidating the therapeutic effect and pharmacological mechanism of YXB capsule in treating RA.</p><p><strong>Methods: </strong>This study identified differentially expressed genes (DEGs) in patients with RA and BS compared to healthy controls using clinical transcriptomics data. Clinical symptoms of RA and BS, and the related genes were collected from the SoFDA and HPO databases. Candidate bioactive constituents in YXB were identified via UPLC-QTOF/MS and evaluated using ADMET rules. Putative targets were predicted, and a network linking disease-related DEGs and drug targets was constructed. Key targets were screened utilizing random walk-with-restart (RWR) algorithms and verified through experiments using rat models of collagen-induced arthritis with BS (CIA-BS model) in vivo.</p><p><strong>Results: </strong>We found 1220 DEGs along with 976 clinical symptom-related genes, as RA with BS-related genes. Chemical profiling identified 193 YXB constituents, with 98 meeting optimal ADMET criteria. We predicted 459 putative targets for these constituents. Network calculations screened 209 key targets, 129 RA with BS-related genes and 92 YXB targets involved in immune inflammation, blood stagnation, and hyperalgesia imbalance. Notably, the SUCNR1/HIF-1α/TRPV1 axis was enriched by YXB targets against RA with BS. Experimentally, YXB inhibited inflamed joint deterioration, including synovial inflammation, cartilage damage and bone erosion, relieving mechanical and cold allodynia hyperglasia. It reversed hemorrheology and vascular function in CIA-BS rats, restoring SDHB and eNOS expression, preventing SDHA, SUCNR1 and HIF-1α activation, reducing SUCN, TNF-α and IL-1β production, and TRPV1 and TRPA1 expression.</p><p><strong>Conclusion: </strong>Our data support YXB's therapeutic effects on aggressive RA-BS by modulating the SUCNR1/HIF-1α/TRPV1 axis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156354"},"PeriodicalIF":6.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984641","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":"Comparative chloroplast genome analyses provide new insights into molecular markers for distinguishing Arnebiae Radix and its substitutes (tribe Lithospermeae, Boraginaceae)","authors":"Sheng Wang ,&nbsp;Yiheng Wang ,&nbsp;Jiahui Sun ,&nbsp;Xingyong Cui ,&nbsp;Enze Li ,&nbsp;Ruishan Wang ,&nbsp;Qi Li ,&nbsp;Pengfei Zhang ,&nbsp;Wenpan Dong ,&nbsp;Lanping Guo ,&nbsp;Luqi Huang","doi":"10.1016/j.phymed.2024.156338","DOIUrl":"10.1016/j.phymed.2024.156338","url":null,"abstract":"<div><h3>Background</h3><div><em>Arnebiae Radix</em> has long been used in traditional medicine for its pleiotropic properties. However, distinguishing <em>Arnebiae Radix</em> from its substitutes or closely related species has been challenging due to limited phenotypic characteristics.</div></div><div><h3>Purpose</h3><div>We aimed to identify the molecular markers for distinguishing <em>Arnebiae Radix</em> from its confusion species.</div></div><div><h3>Study design</h3><div>Chloroplast genome sequences were used to identify the markers.</div></div><div><h3>Methods</h3><div>Chloroplast genomes from 15 species across five genera, including all historically used source plants, were sequenced and assembled.</div></div><div><h3>Results</h3><div>The results revealed significant similarities across all chloroplast genomes in terms of structure, size, gene content, repeat sequences pattens, and codon usage patterns. Phylogenetic analysis showed that the genera <em>Lithospermum, Buglossoides</em>, and <em>Aegonychon</em> formed one clade, while <em>Arnebia guttata, Ar. decumbens</em>, and <em>Ar. euchroma</em> form another. Despite most regions of the chloroplast genomes are highly conserved, three regions—<em>petA-psbJ, ndhF-rpl32</em>, and <em>ycf1</em>—exhibited high variability among difference species, providing high-resolution markers for species identification. Specifically, 376 and 325 species-specific sites were identified in <em>Ar. euchroma</em> and <em>Ar. guttata</em>, respectively. Additionally, four species-specific sites were identified as novel molecular markers, potentially aiding in distinguishing <em>Arnebiae Radix</em> and its confusion or substitute species.</div></div><div><h3>Conclusion</h3><div>This study provided new genetic insights for differentiating <em>Arnebiae Radix</em> and its confusion species, paving the way for further exploration of these medicinal plants.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156338"},"PeriodicalIF":6.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896893","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":"Isobicyclogermacrenal ameliorates hippocampal ferroptosis involvement in neurochemical disruptions and neuroinflammation induced by sleep deprivation in rats","authors":"Ao Yan ,&nbsp;Zhejin Li ,&nbsp;Yuanwei Gao ,&nbsp;Fanglong Hu ,&nbsp;Shuo Han ,&nbsp;Fengjie Liu ,&nbsp;Zhongcheng Liu ,&nbsp;Jinting Chen ,&nbsp;Chunmao Yuan ,&nbsp;Chengyan Zhou","doi":"10.1016/j.phymed.2024.156306","DOIUrl":"10.1016/j.phymed.2024.156306","url":null,"abstract":"<div><h3>Background</h3><div>Sleep deprivation (SLD) is a widespread condition that disrupts physiological functions and may increase mortality risk. Valeriana officinalis, a traditional medicinal herb known for its sedative and hypnotic properties, contains isobicyclogermacrenal (IG), a newly isolated active compound. However, research on the therapeutic potential of IG for treating SLD remains limited.</div></div><div><h3>Methods</h3><div>In this study, IG was extracted and characterized from <em>Valeriana officinalis</em>, and an SLD model was established in rats using p-chlorophenylalanine (PCPA). Behavioral tests and pathological studies were conducted to assess the effects of IG on SLD, and transcriptomic and metabolomic analyses were utilized to investigate its underlying mechanisms.</div></div><div><h3>Results</h3><div>IG administration significantly improved the cognitive performance of SLD rats in behavioral tests and ameliorated histological injuries in the hippocampus and cerebral cortex. IG treatment increased the levels of brain-derived neurotrophic factor (BDNF) and neurotransmitters such as serotonin (5-HT) in SLD rats. Additionally, IG directly targets TFRC, thereby improving iron metabolism in the hippocampus. Comprehensive transcriptomic and metabolomic analyses revealed that the improvements from IG stemmed from the mitigation of abnormalities in iron metabolism, cholesterol metabolism, and glutathione metabolism, leading to reduced oxidative stress, ferroptosis, and neuroinflammation in the hippocampus caused by SLD.</div></div><div><h3>Conclusions</h3><div>Collectively, these findings suggest that IG has the potential to ameliorate neurological damage and cognitive impairment caused by SLD, offering a novel strategy for protection against the adverse effects of SLD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156306"},"PeriodicalIF":6.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794979","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":"Quercetin inhibits hydrogen peroxide-induced cleavage of heat shock protein 90 to prevent glutathione peroxidase 4 degradation via chaperone-mediated autophagy","authors":"Caiwang Peng ,&nbsp;Hengli Li ,&nbsp;Qingling Mao ,&nbsp;Keyan Tang ,&nbsp;Mu Sun ,&nbsp;Qidi Ai ,&nbsp;Yantao Yang ,&nbsp;Fang Liu","doi":"10.1016/j.phymed.2024.156286","DOIUrl":"10.1016/j.phymed.2024.156286","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Oxidative stress is caused by the accumulation of reactive oxygen species (ROS) and the depletion of free radical scavengers, which is closely related to ferroptosis in diseases. Quercetin, as a natural flavonoid compound, has been reported to have multiple pharmacological effects on the basis of its anti-oxidative and anti-ferroptotic activities. This study was designed to explore the specific mechanism of quercetin against ferroptosis induced by hydrogen peroxide (H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The HT22 cells (mouse hippocampal neuronal cells) treated with 40 μg·ml&lt;sup&gt;-1&lt;/sup&gt; H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; were used to investigate the role of ferroptosis in oxidative stress damage and the regulation of quercetin (7.5, 15, 30 μmol·l&lt;sup&gt;-1&lt;/sup&gt;), as evidenced by assessments of cell viability, morphological damage, Fe&lt;sup&gt;2+&lt;/sup&gt; accumulation, and the expressions of ferroptotic-related proteins. The changes in the expression levels of glutathione peroxidase 4 (GPX4), heat shock cognate protein 70 (HSC70), lysosomal-associated membrane protein 2a (LAMP-2a), and heat shock protein (HSP90) were assessed by qPCR, western blotting (WB) and immunofluorescence (IF) assays. Additionally, the interactions of GPX4, HSC70, LAMP-2a, and HSP90 were examined by co-immunoprecipitation (Co-IP) assay to elucidate the impact of quercetin on the degradation pathway of GPX4 and the CMA pathway. To further explore the regulatory mechanism of quercetin, the si-LAMP-2a and HSP90 mutant cells were conducted.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Pretreatment with 30 μmol·l&lt;sup&gt;-1&lt;/sup&gt; quercetin for 6 h significantly enhanced the survival rate (&lt;em&gt;p&lt;/em&gt; &lt; 0.05), maintained cell morphology, and inhibited Fe&lt;sup&gt;2+&lt;/sup&gt; levels in HT22 cells exposed to H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; (40 μg·ml&lt;sup&gt;-1&lt;/sup&gt;). HT22 cells under oxidative stress showed lower expressions of GPX4 and ferritin heavy chain 1 (FTH1), and a higher level of Acyl-CoA synthetase long-chain family member 4 (ACSL4) (&lt;em&gt;p&lt;/em&gt; &lt; 0.05). And quercetin significantly reversed the expressions of these ferroptotic proteins (&lt;em&gt;p&lt;/em&gt; &lt; 0.05). Moreover, the autophagic lysosomal pathway inhibitor CQ effectively increased the expression of GPX4 in oxidative stress cell model. Further study showed that H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; increased the activity of macroautophagy and chaperone-mediated autophagy (CMA), while quercetin notably suppressed the levels of microtubule-associated protein light chain 3 Ⅱ (LC3 Ⅱ), LAMP-2a, and the activity of lysosomes (&lt;em&gt;p&lt;/em&gt; &lt; 0.01). Additionally, quercetin disrupted the interactions of GPX4, HSC70, and LAMP-2a, reduced cellular levels of CMA by decreasing the cleaved HSP90 (c-HSP90), and these effects were reversed in the R347 mutant HT22 cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Quercetin has a significantly protective effect on oxidative stress cell model through the inhibition on ferroptosis, wh","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156286"},"PeriodicalIF":6.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794985","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}