{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:58:35Z","timestamp":1787317115827,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010010","name":"Shanxi Province Science Foundation for Youths","doi-asserted-by":"publisher","award":["201801D221252"],"award-info":[{"award-number":["201801D221252"]}],"id":[{"id":"10.13039\/501100010010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We aimed to study the effects of an ethyl acetate fraction of Physalis alkekengi (PAE) on d-galactose (d-gal)-induced senescence and the underlying mechanism. Firstly, analysis of the phytochemical composition revealed total flavonoids, total phenolics, total saponins, rutin, and luteolin contents of 71.72 \u00b1 2.99 mg rutin equivalents\/g, 40.19 \u00b1 0.47 mg gallic acid equivalents\/g, 128.13 \u00b1 1.04 mg oleanolic acid equivalents\/g, 1.67 \u00b1 0.07 mg\/g and 1.61 \u00b1 0.01 mg\/g, respectively. The mice were treated with d-gal for six weeks, and from the fifth week, the mice were administered with PAE by gavage once a day for five weeks. We found significant d-gal-induced ageing-related changes, such as learning and memory impairment in novel object recognition and Y-maze, fatigue in weight-loaded forced swimming, reduced thymus coefficient, and histopathological injury of the liver, spleen, and hippocampus. The PAE effectively protected from such changes. Further evaluation showed that PAE decreased the senescence-associated \u03b2-galactosidase of the liver, spleen, and hippocampus, as well as the oxidative stress of the liver, plasma, and brain. The abundance of flavonoids, phenols, and saponins in PAE may have contributed to the above results. Overall, this study showed the potential application of PAE for the prevention or treatment of ageing-associated disorders.<\/jats:p>","DOI":"10.3390\/ijms21051836","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T09:26:41Z","timestamp":1583486801000},"page":"1836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Anti-Ageing Effect of Physalis alkekengi Ethyl Acetate Layer on a d-galactose-Induced Mouse Model through the Reduction of Cellular Senescence and Oxidative Stress"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3642-6970","authenticated-orcid":false,"given":"Kaiyue","family":"Sun","sequence":"first","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingting","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heyang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyao","family":"Han","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijiao","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/nature06516","article-title":"The coming acceleration of global population ageing","volume":"451","author":"Lutz","year":"2008","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3389\/fnagi.2017.00298","article-title":"Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome","volume":"9","author":"Hoffman","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1111\/j.1532-5415.2010.03088.x","article-title":"Prevalence and predictors of fatigue among middle-aged and older adults: Evidence from the health and retirement study","volume":"58","author":"Meng","year":"2010","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cell.2017.05.015","article-title":"Senescence in Health and Disease","volume":"169","author":"He","year":"2017","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s10522-018-9763-7","article-title":"Obesity and type-2 diabetes as inducers of premature cellular senescence and ageing","volume":"19","author":"Burton","year":"2018","journal-title":"Biogerontology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"H448","DOI":"10.1152\/ajpheart.00287.2018","article-title":"Cellular senescence links aging and diabetes in cardiovascular disease","volume":"315","author":"Shakeri","year":"2018","journal-title":"Am. J. Physiol Heart Circ. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/d41586-018-01668-0","article-title":"Find drugs that delay many diseases of old age","volume":"554","author":"Bellantuono","year":"2018","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/s41591-018-0092-9","article-title":"Senolytics improve physical function and increase lifespan in old age","volume":"24","author":"Xu","year":"2018","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15691","DOI":"10.1038\/ncomms15691","article-title":"Cellular senescence drives age-dependent hepatic steatosis","volume":"8","author":"Ogrodnik","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/nm.4324","article-title":"Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment","volume":"23","author":"Jeon","year":"2017","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.celrep.2017.12.092","article-title":"Cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathy linked to Parkinson\u2019s disease","volume":"22","author":"Chinta","year":"2018","journal-title":"Cell Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41586-018-0543-y","article-title":"Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline","volume":"562","author":"Bussian","year":"2018","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/nrd.2017.116","article-title":"Senescent cells: An emerging target for diseases of ageing","volume":"16","author":"Childs","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.mad.2016.09.009","article-title":"Interventions for age-related diseases: Shifting the paradigm","volume":"160","author":"Figueira","year":"2016","journal-title":"Mech. Ageing Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/acel.12344","article-title":"The Achilles\u2019 heel of senescent cells: From transcriptome to senolytic drugs","volume":"14","author":"Zhu","year":"2015","journal-title":"Aging Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/nm.4385","article-title":"Targeting cellular senescence prevents age-related bone loss in mice","volume":"23","author":"Farr","year":"2017","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s11523-011-0174-9","article-title":"Common toxicities of mammalian target of rapamycin inhibitors","volume":"6","author":"Soefje","year":"2011","journal-title":"Target Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wang, G.S., and Hoyte, C. Review of Biguanide (Metformin) Toxicity. J. Intensiv. Care Med., 2018.","DOI":"10.1177\/0885066618793385"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imbio.2014.10.004","article-title":"Anti-inflammatory activities of Physalis alkekengi var. franchetii extract through the inhibition of MMP-9 and AP-1 activation","volume":"220","author":"Hong","year":"2015","journal-title":"Immunobiology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"M398","DOI":"10.1111\/j.1750-3841.2011.02213.x","article-title":"Antibacterial activity and mechanism of action of chlorogenic acid","volume":"76","author":"Lou","year":"2011","journal-title":"J. Food Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.phytol.2014.08.004","article-title":"Physalins and withanolides from the fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino and the inhibitory activities against human tumor cells","volume":"10","author":"Li","year":"2014","journal-title":"Phytochem. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.jep.2017.08.022","article-title":"Physalis alkekengi L. var. franchetii (Mast.) Makino: An ethnomedical, phytochemical and pharmacological review","volume":"210","author":"Li","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.fitote.2018.02.015","article-title":"Evaluation of in vitro\/in vivo anti-diabetic effects and identification of compounds from Physalis alkekengi","volume":"127","author":"Hu","year":"2018","journal-title":"Fitoterapia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jep.2016.01.023","article-title":"The ethyl acetate fraction from physalis alkekengi inhibits LPS-induced pro-inflammatory mediators in BV2 cells and inflammatory pain in mice","volume":"181","author":"Moniruzzaman","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s12192-018-0887-0","article-title":"HO-1 dependent antioxidant effects of ethyl acetate fraction from Physalis alkekengi fruit ameliorates scopolamine-induced cognitive impairments","volume":"23","author":"Moniruzzaman","year":"2018","journal-title":"Cell Stress Chaperones"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7108604","DOI":"10.1155\/2018\/7108604","article-title":"Matrine Attenuates D-Galactose-Induced Aging-Related Behavior in Mice via Inhibition of Cellular Senescence and Oxidative Stress","volume":"2018","author":"Sun","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1039\/C7FO01210A","article-title":"Preventive effects of taurine against D-galactose-induced cognitive dysfunction and brain damage","volume":"9","author":"Tu","year":"2018","journal-title":"Food Funct."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.1039\/C6FO01057A","article-title":"Polydatin attenuates D-galactose-induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice","volume":"7","author":"Xu","year":"2016","journal-title":"Food Funct."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10342","DOI":"10.1021\/acs.jafc.9b04614","article-title":"Maltol (3-hydroxy-2-methyl-4-pyrone) slows D-galactose-induced brain aging process by damping the Nrf2\/HO-1-mediated oxidative stress in mice","volume":"67","author":"Sha","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","first-page":"5881","article-title":"Comparison of naturally aging and D-galactose induced aging model in beagle dogs","volume":"14","author":"Ji","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/BF02915139","article-title":"Human hepatocyte polyploidization kinetics in the course of life cycle","volume":"64","author":"Kudryavtsev","year":"1993","journal-title":"Virchows Archiv. B"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109204","DOI":"10.1016\/j.biopha.2019.109204","article-title":"Protective effects of collagen polypeptide from tilapia skin against injuries to the liver and kidneys of mice induced by D-galactose","volume":"117","author":"Li","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.intimp.2018.03.017","article-title":"Protective effects of ginsenoside Rg1 on splenocytes and thymocytes in an aging rat model induced by d-galactose. Int","volume":"58","author":"Sun","year":"2018","journal-title":"Immunopharmacol"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.1007\/s11064-016-2022-x","article-title":"Protective effect of hyperbaric oxygen on cognitive impairment induced by D-galactose in mice","volume":"41","author":"Chen","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_35","first-page":"961","article-title":"The signals and pathways activating cellular senescence","volume":"37","author":"Ittai","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.pnpbp.2004.12.008","article-title":"Further evidence for the cholinergic hypothesis of aging and dementia from the canine model of aging","volume":"29","author":"Araujo","year":"2005","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.semcdb.2012.04.003","article-title":"Oxidative stress and adult neurogenesis-effects of radiation and superoxide dismutase deficiency","volume":"23","author":"Huang","year":"2012","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Tung, Y.T., Wu, M.F., Lee, M.C., Wu, J.H., Huang, C.C., and Huang, W.C. (2019). Antifatigue Activity and Exercise Performance of Phenolic-Rich Extracts from Calendula officinalis, Ribes nigrum, and Vaccinium myrtillus. Nutrients, 11.","DOI":"10.3390\/nu11081715"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3159358","DOI":"10.1155\/2017\/3159358","article-title":"Antifatigue Effect of Luteolin-6-C-Neohesperidoside on Oxidative Stress Injury Induced by Forced Swimming of Rats through Modulation of Nrf2\/ARE Signaling Pathways","volume":"2017","author":"Duan","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1093\/rheumatology\/keq454","article-title":"Biological mechanisms of chronic fatigue","volume":"50","author":"Norheim","year":"2011","journal-title":"Rheumatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10564","DOI":"10.1093\/nar\/gkx684","article-title":"Replication stress-induced endogenous DNA damage drives cellular senescence induced by a sub-lethal oxidative stress","volume":"45","author":"Venkatachalam","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.bbamcr.2011.01.029","article-title":"Mitochondrial longevity pathways","volume":"1813","author":"Vendelbo","year":"2011","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"320513","DOI":"10.1155\/2014\/320513","article-title":"Saponins from Aralia taibaiensis Attenuate D-Gal-Induced Aging in Rats by Activating FOXO3a and Nrf2 Pathways","volume":"2014","author":"Li","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1016\/j.foodchem.2012.06.048","article-title":"Antioxidant activity of Lactobacillus plantarum strains isolated from traditional Chinese fermented foods","volume":"135","author":"Li","year":"2012","journal-title":"Food Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jchromb.2005.06.035","article-title":"Determination of malondialdehyde (MDA) by high-performance liquid chromatography in serum and liver as a biomarker for oxidative stress. Application to a rat model for hypercholesterolemia and evaluation of the effect of diets rich in phenolic antioxidants from fruits","volume":"827","author":"Mateos","year":"2005","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.intimp.2018.11.026","article-title":"Pseudoginsenoside-F11 alleviates cognitive deficits and Alzheimer\u2019s disease-type pathologies in SAMP8 mice","volume":"67","author":"Zhang","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1089\/rej.2015.1708","article-title":"Dietary Luteolin Reduces Proinflammatory Microglia in the Brain of Senescent Mice","volume":"19","author":"Burton","year":"2016","journal-title":"Rejuvenation Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainresbull.2015.09.002","article-title":"Luteolin as an anti-inflammatory and neuroprotective agent: A brief review","volume":"119","author":"Nabavi","year":"2015","journal-title":"Brain Res. Bull."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1039\/C5FO01036E","article-title":"Rutin protects against aging-related metabolic dysfunction","volume":"7","author":"Li","year":"2016","journal-title":"Food Funct."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1111\/bph.13631","article-title":"Anti-ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: Pharmacological mechanisms and implications for drug discovery","volume":"174","author":"Shen","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"110781","DOI":"10.1016\/j.fct.2019.110781","article-title":"Protective effects of raspberry on the oxidative damage in HepG2 cells through Keap1\/Nrf2-dependent signaling pathway","volume":"133","author":"Chen","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"103633","DOI":"10.1016\/j.jff.2019.103633","article-title":"Effects of high-pressure homogenization, thermal processing, and milk matrix on the in vitro bioaccessibility of phenolic compounds in pomelo and kiwi juices","volume":"64","author":"Quan","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jff.2016.01.028","article-title":"Characterization of active constituents in Pyracantha fortuneana fruit extract and their effects on hyperlipidaemia, obesity, and oxidative stress in rodents","volume":"22","author":"Xu","year":"2016","journal-title":"J. Funct. Foods"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s11011-018-0335-y","article-title":"Neuroprotective effects of matrine on scopolamine-induced amnesia via inhibition of AChE\/BuChE and oxidative stress","volume":"34","author":"Sun","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"562345","DOI":"10.1155\/2015\/562345","article-title":"Antifatigue activity of liquid cultured tricholoma matsutake mycelium partially via regulation of antioxidant pathway in mouse","volume":"2015","author":"Li","year":"2015","journal-title":"BioMed Res. Int."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/5\/1836\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:04:51Z","timestamp":1760173491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/5\/1836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,6]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["ijms21051836"],"URL":"https:\/\/doi.org\/10.3390\/ijms21051836","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,6]]}}}