{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:14:35Z","timestamp":1768504475579,"version":"3.49.0"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Renshen Yangrong decoction (RSYRD) has been shown therapeutic effects on secondary malaise and fatigue (SMF). However, to date, its bioactive ingredients and potential targets remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>The purpose of this study is to assess the potential ingredients and targets of RSYRD on SMF through a comprehensive strategy integrating network pharmacology, Mendelian randomization as well as molecular docking verification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Search for potential active ingredients and corresponding protein targets of RSYRD on TCMSP and BATMAN-TCM for network pharmacology analysis. Mendelian randomization (MR) was performed to find therapeutic targets for SMF. The eQTLGen Consortium (sample sizes: 31,684) provided data on cis-expression quantitative trait loci (cis-eQTL, exposure). The summary data on SMF (outcome) from genome-wide association studies (GWAS) were gathered from the MRC-IEU Consortium (sample sizes: 463,010). We built a target interaction network between the probable active ingredient targets of RSYRD and the therapeutic targets of SMF. We next used drug prediction and molecular docking to confirm the therapeutic value of the therapeutic targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In RSYRD, network pharmacology investigations revealed 193 possible active compounds and 234 associated protein targets. The genetically predicted amounts of 176 proteins were related to SMF risk in the MR analysis. Thirty-seven overlapping targets for RSYRD in treating SMF, among which six (NOS3, GAA, IMPA1, P4HTM, RB1, and SLC16A1) were prioritized with the most convincing evidence. Finally, the 14 active ingredients of RSYRD were identified as potential drug molecules. The strong affinity between active components and putative protein targets was established by molecular docking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study revealed several active components and possible RSYRD protein targets for the therapy of SMF and provided novel insights into the feasibility of using Mendelian randomization for causal inference between Chinese medical formula and disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2024.1404123","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T05:10:26Z","timestamp":1718860226000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Renshen Yangrong decoction for secondary malaise and fatigue: network pharmacology and Mendelian randomization study"],"prefix":"10.3389","volume":"11","author":[{"given":"Fanghan","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanchun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingliang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aixiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.mcna.2020.09.007","article-title":"Approach to fatigue: best practice","volume":"105","author":"Dukes","year":"2021","journal-title":"Med Clin North Am"},{"key":"ref2","first-page":"58","article-title":"Fatigue in adults: evaluation and management","volume":"108","author":"Latimer","year":"2023","journal-title":"Am Fam Physician"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3389\/fneur.2015.00021","article-title":"Fatigue in multiple sclerosis: a look at the role of poor sleep","volume":"6","author":"Strober","year":"2015","journal-title":"Front Neurol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1007\/s00415-012-6828-4","article-title":"Clinical determinants of primary and secondary fatigue in patients with Parkinson\u2019s disease","volume":"260","author":"Skorvanek","year":"2013","journal-title":"J Neurol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"P1","DOI":"10.1164\/rccm.2075P1","article-title":"What is fatigue?","volume":"207","author":"Van Herck","year":"2023","journal-title":"Am J Respir Crit Care Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1001\/jamaoncol.2016.6914","article-title":"Comparison of pharmaceutical, psychological, and exercise treatments for cancer-related fatigue: a meta-analysis","volume":"3","author":"Mustian","year":"2017","journal-title":"JAMA Oncol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"CD008322","DOI":"10.1002\/14651858.CD008322.pub2","article-title":"Non-pharmacological interventions for fatigue in rheumatoid arthritis","author":"Cramp","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"110524","DOI":"10.1016\/j.jpsychores.2021.110524","article-title":"A systematic review of psychological treatments to manage fatigue in patients with inflammatory bowel disease","volume":"147","author":"Emerson","year":"2021","journal-title":"J Psychosom Res"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s12866-023-02896-9","article-title":"Diarrhea accompanies intestinal inflammation and intestinal mucosal microbiota dysbiosis during fatigue combined with a high-fat diet","volume":"23","author":"Liu","year":"2023","journal-title":"BMC Microbiol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.nmd.2020.06.010","article-title":"Fatigue in patients with myasthenia gravis. A systematic review of the literature","volume":"30","author":"Ruiter","year":"2020","journal-title":"Neuromuscul Disord"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1055\/a-1524-1935","article-title":"Effect of exercise on fatigue in multiple sclerosis patients: a network meta-analysis","volume":"42","author":"Chen","year":"2021","journal-title":"Int J Sports Med"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/j.apmr.2020.06.019","article-title":"Effectiveness of exercise on fatigue and sleep quality in fibromyalgia: a systematic review and meta-analysis of randomized trials","volume":"102","author":"Estevez-Lopez","year":"2021","journal-title":"Arch Phys Med Rehabil"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s13075-018-1671-3","article-title":"Physical activity is related to function and fatigue but not pain in women with fibromyalgia: baseline analyses from the fibromyalgia activity study with TENS (FAST)","volume":"20","author":"Merriwether","year":"2018","journal-title":"Arthritis Res Ther"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"k851","DOI":"10.1136\/bmj.k851","article-title":"Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial","volume":"360","author":"Wang","year":"2018","journal-title":"BMJ"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00520-017-3955-6","article-title":"Effects of acupuncture on cancer-related fatigue: a meta-analysis","volume":"26","author":"Zhang","year":"2018","journal-title":"Support Care Cancer"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1002\/cncr.31064","article-title":"Massage therapy decreases cancer-related fatigue: results from a randomized early phase trial","volume":"124","author":"Kinkead","year":"2018","journal-title":"Cancer"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e2300452","DOI":"10.1002\/mnfr.202300452","article-title":"Association of short-chain fatty acids with gut microbiota and lipid metabolism in mice with diarrhea induced by high-fat diet in a fatigued state","volume":"67","author":"Qiao","year":"2023","journal-title":"Mol Nutr Food Res"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"100092","DOI":"10.1016\/j.esmoop.2021.100092","article-title":"Cancer cachexia in adult patients: ESMO clinical practice guidelines","volume":"6","author":"Arends","year":"2021","journal-title":"ESMO Open"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/S1474-4422(20)30354-9","article-title":"Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial","volume":"20","author":"Nourbakhsh","year":"2021","journal-title":"Lancet Neurol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1186\/s12905-022-01824-9","article-title":"Safety and efficacy of Ninjin\u2019yoeito along with iron supplementation therapy for preoperative anemia, fatigue, and anxiety in patients with gynecological disease: an open-label, single-center, randomized phase-II trial","volume":"22","author":"Yagi","year":"2022","journal-title":"BMC Womens Health"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1111\/pcn.12667","article-title":"Apathy and fatigue in autistic spectrum disorder improved by Japanese herbal medicine: TSUMURA Ninjin\u2019yoeito extract","volume":"72","author":"Sato","year":"2018","journal-title":"Psychiatry Clin Neurosci"},{"key":"ref22","first-page":"1033","article-title":"The effect of Ninjinyoeito for patients undergoing chemotherapy","volume":"46","author":"Fukuhara","year":"2019","journal-title":"Gan To Kagaku Ryoho"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"72","DOI":"10.3389\/fnut.2018.00072","article-title":"Combined use of Ninjin\u2019yoeito improves subjective fatigue caused by lenalidomide in patients with multiple myeloma: a retrospective study","volume":"5","author":"Ito","year":"2018","journal-title":"Front Nutr"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"100605","DOI":"10.1016\/j.curtheres.2020.100605","article-title":"Impact of Ninjin\u2019yoeito on fatigue in patients receiving nab-paclitaxel plus gemcitabine therapy: a prospective, single-arm, phase II open label, nonrandomized, historically-controlled study","volume":"93","author":"Okada","year":"2020","journal-title":"Curr Ther Res Clin Exp"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1089\/acm.2014.0211","article-title":"Ren Shen Yangrong Tang for fatigue in cancer survivors: a phase I\/II open-label study","volume":"21","author":"Xu","year":"2015","journal-title":"J Altern Complement Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3389\/fnut.2019.00014","article-title":"Safety and effectiveness of Ninjin\u2019yoeito: a utilization study in elderly patients","volume":"6","author":"Suzuki","year":"2019","journal-title":"Front Nutr"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1016\/j.jpainsymman.2019.10.018","article-title":"A phase II randomized controlled trial of Renshen Yangrong Tang herbal extract granules for fatigue reduction in cancer survivors","volume":"59","author":"Xu","year":"2020","journal-title":"J Pain Symptom Manag"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"102136","DOI":"10.1016\/j.npep.2021.102136","article-title":"Ninjinyoeito improves anxiety behavior in neuropeptide Y deficient zebrafish","volume":"87","author":"Kawabe","year":"2021","journal-title":"Neuropeptides"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.3389\/fphar.2018.01216","article-title":"Ninjinyoeito improves behavioral abnormalities and hippocampal neurogenesis in the corticosterone model of depression","volume":"9","author":"Murata","year":"2018","journal-title":"Front Pharmacol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1097\/WNR.0000000000001667","article-title":"Ninjin\u2019yoeito, a traditional Japanese Kampo medicine, suppresses the onset of anhedonia induced by dysfunction in the striatal dopamine receptor type 2-expressing medium spiny neurons","volume":"32","author":"Oizumi","year":"2021","journal-title":"Neuroreport"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/psyg.12125","article-title":"Effect of Ninjin\u2019yoeito, a Kampo (traditional Japanese) medicine, on cognitive impairment and depression in patients with Alzheimer\u2019s disease: 2 years of observation","volume":"16","author":"Kudoh","year":"2016","journal-title":"Psychogeriatrics"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e1008489","DOI":"10.1371\/journal.pgen.1008489","article-title":"Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval","volume":"15","author":"King","year":"2019","journal-title":"PLoS Genet"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"18911","DOI":"10.1038\/s41598-019-54849-w","article-title":"Improving the odds of drug development success through human genomics: modelling study","volume":"9","author":"Hingorani","year":"2019","journal-title":"Sci Rep"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.1038\/s41467-020-16969-0","article-title":"Genetic drug target validation using Mendelian randomisation","volume":"11","author":"Schmidt","year":"2020","journal-title":"Nat Commun"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"eaag1166","DOI":"10.1126\/scitranslmed.aag1166","article-title":"The druggable genome and support for target identification and validation in drug development","volume":"9","author":"Finan","year":"2017","journal-title":"Sci Transl Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1038\/s41588-022-01213-w","article-title":"Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis","volume":"54","author":"Ishigaki","year":"2022","journal-title":"Nat Genet"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1001\/jamapsychiatry.2021.0005","article-title":"Association of antihypertensive drug target genes with psychiatric disorders: a Mendelian randomization study","volume":"78","author":"Chauquet","year":"2021","journal-title":"JAMA Psychiatry"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1093\/eurheartj\/ehaa972","article-title":"Metabolic profiling of angiopoietin-like protein 3 and 4 inhibition: a drug-target Mendelian randomization analysis","volume":"42","author":"Wang","year":"2021","journal-title":"Eur Heart J"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.tips.2021.11.004","article-title":"Network pharmacology: curing causal mechanisms instead of treating symptoms","volume":"43","author":"Nogales","year":"2022","journal-title":"Trends Pharmacol Sci"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"4331","DOI":"10.3390\/ijms20184331","article-title":"Molecular docking: shifting paradigms in drug discovery","volume":"20","author":"Pinzi","year":"2019","journal-title":"Int J Mol Sci"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"D1110","DOI":"10.1093\/nar\/gkad926","article-title":"BATMAN-TCM 2.0: an enhanced integrative database for known and predicted interactions between traditional Chinese medicine ingredients and target proteins","volume":"52","author":"Kong","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1758-2946-6-13","article-title":"TCMSP: a database of systems pharmacology for drug discovery from herbal medicines","volume":"6","author":"Ru","year":"2014","journal-title":"J Cheminform"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1038\/s41588-021-00913-z","article-title":"Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression","volume":"53","author":"Vosa","year":"2021","journal-title":"Nat Genet"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1136\/jnnp-2023-331142","article-title":"Systematic druggable genome-wide Mendelian randomisation identifies therapeutic targets for Alzheimer\u2019s disease","volume":"94","author":"Su","year":"2023","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat Genet"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1002\/art.42304","article-title":"Telomere length and development of systemic lupus erythematosus: a Mendelian randomization study","volume":"74","author":"Wang","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"eLife"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1186\/s13059-019-1758-4","article-title":"Cytoscape automation: empowering workflow-based network analysis","volume":"20","author":"Otasek","year":"2019","journal-title":"Genome Biol"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1093\/bioinformatics\/btt285","article-title":"Pathview: an R\/Bioconductor package for pathway-based data integration and visualization","volume":"29","author":"Luo","year":"2013","journal-title":"Bioinformatics"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.1093\/bioinformatics\/btv313","article-title":"DSigDB: drug signatures database for gene set analysis","volume":"31","author":"Yoo","year":"2015","journal-title":"Bioinformatics"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"23","DOI":"10.5582\/ddt.2015.01004","article-title":"Chemical constituents and bioactivities of Panax ginseng (C. A. Mey.)","volume":"9","author":"Ru","year":"2015","journal-title":"Drug Discov Ther"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"952061","DOI":"10.3389\/fphar.2022.952061","article-title":"The chemistry and efficacy benefits of polysaccharides from Atractylodes macrocephala Koidz","volume":"13","author":"Liu","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"565","DOI":"10.5582\/bst.2017.01218","article-title":"Induction of apoptosis by ethanol extract of Citrus unshiu Markovich peel in human bladder cancer T24 cells through ROS-mediated inactivation of the PI3K\/Akt pathway","volume":"11","author":"Ahn","year":"2017","journal-title":"Biosci Trends"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"113626","DOI":"10.1016\/j.biopha.2022.113626","article-title":"Citri Reticulatae Pericarpium (Chenpi): a multi-efficacy pericarp in treating cardiovascular diseases","volume":"154","author":"Zou","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"115594","DOI":"10.1016\/j.jep.2022.115594","article-title":"Licorice: resources, applications in ancient and modern times","volume":"298","author":"Ding","year":"2022","journal-title":"J Ethnopharmacol"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"505249","DOI":"10.3389\/fphar.2020.505249","article-title":"Phytochemistry and pharmacological activities of Wolfiporia Cocos (F.A. Wolf) Ryvarden & Gilb","volume":"11","author":"Nie","year":"2020","journal-title":"Front Pharmacol"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"868","DOI":"10.14336\/AD.2017.0816","article-title":"Anti-aging implications of Astragalus membranaceus (Huangqi): a well-known Chinese tonic","volume":"8","author":"Liu","year":"2017","journal-title":"Aging Dis"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1089\/jmf.2014.3144","article-title":"Differences in the chemical profiles and biological activities of Paeonia lactiflora and Paeonia obovata","volume":"18","author":"Bae","year":"2015","journal-title":"J Med Food"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"116952","DOI":"10.1016\/j.jep.2023.116952","article-title":"Therapeutic potential of traditional Chinese medicine for interstitial lung disease","volume":"318","author":"Zhou","year":"2024","journal-title":"J Ethnopharmacol"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"115809","DOI":"10.1016\/j.biopha.2023.115809","article-title":"Progress of research into the pharmacological effect and clinical application of the traditional Chinese medicine Rehmanniae radix","volume":"168","author":"Jia","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"620","DOI":"10.3390\/antiox10040620","article-title":"Antioxidant effects of Schisandra chinensis fruits and their active constituents","volume":"10","author":"Kopustinskiene","year":"2021","journal-title":"Antioxidants"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.2174\/1389557521666210405160323","article-title":"Anticancer potential of coumarin and its derivatives","volume":"21","author":"Bhattarai","year":"2021","journal-title":"Mini Rev Med Chem"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"105697","DOI":"10.1016\/j.phrs.2021.105697","article-title":"Saponins isolated from radix polygalae extent lifespan by modulating complement C3 and gut microbiota","volume":"170","author":"Zeng","year":"2021","journal-title":"Pharmacol Res"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s13020-020-00370-6","article-title":"What we already know about rhubarb: a comprehensive review","volume":"15","author":"Xiang","year":"2020","journal-title":"Chin Med"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1053\/j.semdp.2019.02.001","article-title":"Paraneoplastic disorders associated with miscellaneous neoplasms with focus on selected soft tissue and undifferentiated\/rhabdoid malignancies","volume":"36","author":"Agaimy","year":"2019","journal-title":"Semin Diagn Pathol"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"3880","DOI":"10.1039\/D3FO00378G","article-title":"Gut content microbiota dysbiosis and dysregulated lipid metabolism in diarrhea caused by high-fat diet in a fatigued state","volume":"14","author":"Qiao","year":"2023","journal-title":"Food Funct"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"e28633","DOI":"10.1097\/MD.0000000000028633","article-title":"Astragalus membranaceus (Huang Qi) for cancer-related fatigue: a protocol for systematic review and meta-analysis","volume":"101","author":"Dong","year":"2022","journal-title":"Medicine"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1016\/j.jep.2016.10.058","article-title":"Effects of the traditional Chinese herb Astragalus membranaceus in patients with poststroke fatigue: a double-blind, randomized, controlled preliminary study","volume":"194","author":"Liu","year":"2016","journal-title":"J Ethnopharmacol"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s11011-019-00483-4","article-title":"Adjuvant therapy with Astragalus membranaceus for post-stroke fatigue: a systematic review","volume":"35","author":"Xu","year":"2020","journal-title":"Metab Brain Dis"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1089\/acm.2017.0361","article-title":"Ginseng as a treatment for fatigue: a systematic review","volume":"24","author":"Arring","year":"2018","journal-title":"J Altern Complement Med"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.3346\/jkms.2016.31.12.1879","article-title":"Efficacy of ginseng supplements on fatigue and physical performance: a meta-analysis","volume":"31","author":"Bach","year":"2016","journal-title":"J Korean Med Sci"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.6004\/jnccn.2017.0149","article-title":"Randomized, placebo-controlled trial of Panax ginseng for cancer-related fatigue in patients with advanced cancer","volume":"15","author":"Yennurajalingam","year":"2017","journal-title":"J Natl Compr Cancer Netw"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1007\/s00432-020-03300-z","article-title":"A randomized, double-blind, placebo controlled, phase II study to evaluate the efficacy of ginseng in reducing fatigue in patients treated for head and neck cancer","volume":"146","author":"Guglielmo","year":"2020","journal-title":"J Cancer Res Clin Oncol"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1089\/jicm.2022.0532","article-title":"Ginseng and ginseng herbal formulas for symptomatic Management of Fatigue: a systematic review and meta-analysis","volume":"29","author":"Li","year":"2023","journal-title":"J Integr Complement Med"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"104409","DOI":"10.1016\/j.phrs.2019.104409","article-title":"Natural medicines for the treatment of fatigue: bioactive components, pharmacology, and mechanisms","volume":"148","author":"Luo","year":"2019","journal-title":"Pharmacol Res"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"115453","DOI":"10.1016\/j.biopha.2023.115453","article-title":"Two-month period of 500 mg lecithin-based delivery form of quercetin daily dietary supplementation counterbalances chronic fatigue symptoms: a double-blind placebo controlled clinical trial","volume":"167","author":"Rondanelli","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"153218","DOI":"10.1016\/j.phymed.2020.153218","article-title":"Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: a comparative, randomized, double-blind, placebo-controlled clinical trial","volume":"70","author":"Saghatelyan","year":"2020","journal-title":"Phytomedicine"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"3090","DOI":"10.3390\/nu13093090","article-title":"The effects of Korean red ginseng on biological aging and antioxidant capacity in postmenopausal women: a double-blind randomized controlled study","volume":"13","author":"Chung","year":"2021","journal-title":"Nutrients"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"528","DOI":"10.7150\/ijms.8220","article-title":"Rutin, a flavonoid and principal component of Saussurea involucrata, attenuates physical fatigue in a forced swimming mouse model","volume":"11","author":"Su","year":"2014","journal-title":"Int J Med Sci"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.tem.2023.01.005","article-title":"Efficacy evaluation, active ingredients, and multitarget exploration of herbal medicine","volume":"34","author":"Ren","year":"2023","journal-title":"Trends Endocrinol Metab"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.phrs.2016.06.018","article-title":"Network pharmacology of cancer: from understanding of complex interactomes to the design of multi-target specific therapeutics from nature","volume":"111","author":"Poornima","year":"2016","journal-title":"Pharmacol Res"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/S1875-5364(22)60180-8","article-title":"Identification of multi-target anti-cancer agents from TCM formula by in silico prediction and in vitro validation","volume":"20","author":"Zhang","year":"2022","journal-title":"Chin J Nat Med"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.1056\/NEJMoa1407778","article-title":"Monocarboxylate transporter 1 deficiency and ketone utilization","volume":"371","author":"van Hasselt","year":"2014","journal-title":"N Engl J Med"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"e141964","DOI":"10.1172\/JCI141964","article-title":"Macrophage monocarboxylate transporter 1 promotes peripheral nerve regeneration after injury in mice","volume":"131","author":"Jha","year":"2021","journal-title":"J Clin Invest"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1038\/nm.4128","article-title":"Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity","volume":"22","author":"Eichner","year":"2016","journal-title":"Nat Med"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.cmet.2018.03.008","article-title":"The science and translation of lactate shuttle theory","volume":"27","author":"Brooks","year":"2018","journal-title":"Cell Metab"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/s41392-022-01151-3","article-title":"Lactate metabolism in human health and disease","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/s42255-020-0243-4","article-title":"Lactate: the ugly duckling of energy metabolism","volume":"2","author":"Rabinowitz","year":"2020","journal-title":"Nat Metab"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1152\/japplphysiol.01057.2004","article-title":"Monocarboxylate transporters, blood lactate removal after supramaximal exercise, and fatigue indexes in humans","volume":"98","author":"Thomas","year":"1985","journal-title":"J Appl Physiol"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s13205-023-03491-5","article-title":"The diarrheal mechanism of mice with a high-fat diet in a fatigued state is associated with intestinal mucosa microbiota","volume":"13","author":"Liu","year":"2023","journal-title":"3 Biotech"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"292","DOI":"10.21037\/atm.2019.05.29","article-title":"Pompe disease: what are we missing?","volume":"7","author":"Schoser","year":"2019","journal-title":"Ann Transl Med"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1007\/s00415-006-0434-2","article-title":"Fatigue: an important feature of late-onset Pompe disease","volume":"254","author":"Hagemans","year":"2007","journal-title":"J Neurol"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1007\/s40265-021-01600-3","article-title":"Avalglucosidase alfa: first Approval","volume":"81","author":"Dhillon","year":"2021","journal-title":"Drugs"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1002\/jimd.12607","article-title":"Physical training and high-protein diet improved muscle strength, parent-reported fatigue, and physical quality of life in children with Pompe disease","volume":"46","author":"Scheffers","year":"2023","journal-title":"J Inherit Metab Dis"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.niox.2016.08.004","article-title":"Clinical and pharmacogenetic impact of endothelial nitric oxide synthase polymorphisms on cardiovascular diseases","volume":"63","author":"Oliveira-Paula","year":"2017","journal-title":"Nitric Oxide"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.2217\/pgs-2018-0098","article-title":"Pharmacogenetic relevance of endothelial nitric oxide synthase polymorphisms and gene interactions","volume":"19","author":"Luizon","year":"2018","journal-title":"Pharmacogenomics"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.redox.2015.08.009","article-title":"The dual role of iNOS in cancer","volume":"6","author":"Vannini","year":"2015","journal-title":"Redox Biol"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1089\/ars.2016.6630","article-title":"Nitric oxide regulates skeletal muscle fatigue, fiber type, microtubule organization, and mitochondrial ATP synthesis efficiency through cGMP-dependent mechanisms","volume":"26","author":"Moon","year":"2017","journal-title":"Antioxid Redox Signal"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1172\/JCI38618","article-title":"NO more muscle fatigue","volume":"119","author":"Heydemann","year":"2009","journal-title":"J Clin Invest"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"215870","DOI":"10.1016\/j.canlet.2022.215870","article-title":"Novel insights into RB1 mutation","volume":"547","author":"Yao","year":"2022","journal-title":"Cancer Lett"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"4205","DOI":"10.1038\/s41467-020-18020-8","article-title":"GLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer","volume":"11","author":"Wu","year":"2020","journal-title":"Nat Commun"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2024.1404123\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T05:10:29Z","timestamp":1718860229000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2024.1404123\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,20]]},"references-count":103,"alternative-id":["10.3389\/fnut.2024.1404123"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2024.1404123","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,20]]},"article-number":"1404123"}}