{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:06:14Z","timestamp":1790730374350,"version":"4.1.0"},"reference-count":112,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874365"],"award-info":[{"award-number":["81874365"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703725"],"award-info":[{"award-number":["81703725"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sichuan Science and Technology Program","award":["2019YJ0492"],"award-info":[{"award-number":["2019YJ0492"]}]},{"DOI":"10.13039\/501100011930","name":"Beijing Medical and Health Foundation","doi-asserted-by":"publisher","award":["YWJKJJHKYJJ-B20645FN"],"award-info":[{"award-number":["YWJKJJHKYJJ-B20645FN"]}],"id":[{"id":"10.13039\/501100011930","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chengdu University of TCM Grant","award":["QNXZ2018025"],"award-info":[{"award-number":["QNXZ2018025"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Chin Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>With the advanced discoveries in the field of pathogenesis, a series of cerebral diseases, such as cerebral ischaemia, Alzheimer's disease, and depression, have been found to have multiple signalling targets in the microenvironment. Only a few existing agents have been shown to have curative effects due to this specific circumstance. In recent decades, active ingredients isolated from natural plants have been shown to be crucial for original drug development. Geniposide, mainly extracted from<jats:italic>Gardenia jasminoides<\/jats:italic>Ellis, is representative of these natural products. Geniposide demonstrates various biological activities in the treatment of cerebral, cardiovascular, hepatic, tumorous, and other diseases. The multiple protective effects of geniposide on the brain have especially drawn increasing attention. Thus, this article specifically reviews the characteristics of current models of cerebral ischaemia and illustrates the possible effects of geniposide and its pathogenetic mechanisms on these models. Geniposide has been shown to significantly reduce the area of cerebral infarction and alleviate neuronal damage and necrosis mainly by inhibiting inflammatory signals, including NLRP3, TNF-\u03b1, IL-6, and IL-1\u03b2. Neuronal protection was also involved in activating the PI3K\/Akt and Wnt\/catenin pathways. Geniposide was able to increase autophagy and inhibit apoptosis by regulating the function of mTOR in treating Alzheimer's disease. Geniposide has also been shown to act as a glucagon-like peptide-1 receptor (GLP-1R) agonist to reduce amyloid plaques and inhibit oxidative stress to alleviate memory impairment as well as synaptic loss. Moreover, geniposide has been shown to exert antidepressant effects primarily by regulating the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis. Detailed explorations have shown that the biological activities of inhibiting inflammatory cytokine secretion, alleviating oxidative stress, and suppressing mitochondrial damage are also involved in the mechanism of action of geniposide. Therefore, geniposide is a promising agent awaiting further exploration for the treatment of cerebral diseases via various phenotypes or signalling pathways.<\/jats:p>","DOI":"10.1186\/s13020-021-00486-3","type":"journal-article","created":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T10:02:37Z","timestamp":1630144957000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["The emerging possibility of the use of geniposide in the treatment of cerebral diseases: a review"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2017-7631","authenticated-orcid":false,"given":"Wenwen","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qichao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linbo","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinxiao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"key":"486_CR1","first-page":"407","volume":"70","author":"J Ziemska","year":"2019","unstructured":"Ziemska J, Szynal T, Maza\u0144ska M, Solecka J. Natural medicinal resources and their therapeutic applications. Rocz Panstw Zakl Hig. 2019;70:407\u201313.","journal-title":"Rocz Panstw Zakl Hig."},{"key":"486_CR2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13020-019-0228-y","volume":"14","author":"W Wang","year":"2016","unstructured":"Wang W, Liang YS. Artemisinin: a wonder drug from Chinese natural medicines. Chin J Nat Med. 2016;14:5\u20136.","journal-title":"Chin J Nat Med."},{"key":"486_CR3","doi-asserted-by":"publisher","first-page":"112829","DOI":"10.1016\/j.jep.2020.112829","volume":"257","author":"L Chen","year":"2020","unstructured":"Chen L, Li M, Yang Z, Tao W, Wang P, Tian X, et al. Gardenia jasminoides Ellis: Ethnopharmacology, phytochemistry, and pharmacological and industrial applications of an important traditional Chinese medicine. J Ethnopharmacol. 2020;257:112829.","journal-title":"J Ethnopharmacol."},{"key":"486_CR4","doi-asserted-by":"publisher","first-page":"180","DOI":"10.3389\/fphar.2019.00180","volume":"10","author":"Y Cui","year":"2019","unstructured":"Cui Y, Wang Q, Wang M, Jia J, Wu R. Gardenia decoction prevent intestinal mucosal injury by inhibiting pro-inflammatory cytokines and NF-\u03baB signaling. Front Pharmacol. 2019;10:180.","journal-title":"Front Pharmacol."},{"key":"486_CR5","doi-asserted-by":"publisher","first-page":"4360","DOI":"10.3892\/mmr.2017.6542","volume":"15","author":"S Chen","year":"2017","unstructured":"Chen S, Sun P, Zhao X, Yi R, Qian J, Shi Y, et al. Gardenia jasminoides has therapeutic effects on L-NNA-induced hypertension in vivo. Mol Med Rep. 2017;15:4360\u201373.","journal-title":"Mol Med Rep"},{"key":"486_CR6","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jfda.2016.11.005","volume":"25","author":"W Xiao","year":"2017","unstructured":"Xiao W, Li S, Wang S, Ho CT. Chemistry and bioactivity of Gardenia jasminoides. J Food Drug Anal. 2017;25:43\u201361.","journal-title":"J Food Drug Anal"},{"key":"486_CR7","doi-asserted-by":"publisher","first-page":"102248","DOI":"10.1016\/j.ctim.2019.102248","volume":"48","author":"KD Li","year":"2020","unstructured":"Li KD, Wang QS, Zhang WW, Zhang WY, Fu SN, Xu D, et al. Gardenia fructus antidepressant formula for depression in diabetes patients: a systematic review and meta-analysis. Complement Ther Med. 2020;48:102248.","journal-title":"Complement Ther Med."},{"key":"486_CR8","doi-asserted-by":"publisher","first-page":"196","DOI":"10.3390\/nu12010196","volume":"12","author":"HI Kim","year":"2020","unstructured":"Kim HI, Hong SH, Ku JM, Kim MJ, Ju SW, Chang SW, et al. Gardenia jasminoides enhances CDDP-induced apoptosis of glioblastoma cells via AKT\/mTOR pathway while protecting death of astrocytes. Nutrients. 2020;12:196.","journal-title":"Nutrients"},{"key":"486_CR9","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3390\/biomedicines6020039","volume":"6","author":"S Habtemariam","year":"2018","unstructured":"Habtemariam S, Lentini G. Plant-derived anticancer agents: Lessons from the pharmacology of geniposide and its aglycone, genipin. Biomedicines. 2018;6:39.","journal-title":"Biomedicines."},{"key":"486_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/molecules22101689","volume":"22","author":"M Shan","year":"2017","unstructured":"Shan M, Yu S, Yan H, Guo S, Xiao W, Wang Z, et al. A review on the phytochemistry, pharmacology, pharmacokinetics and toxicology of geniposide, a natural product. Molecules. 2017;22:1\u201329.","journal-title":"Molecules"},{"key":"486_CR11","unstructured":"Hasso AN, Stringer WA, Brown KD. Cerebral ischemia and infarction. Neuroimaging Clin; 1994. 733\u201352."},{"key":"486_CR12","first-page":"7480512","volume":"2019","author":"N Li","year":"2019","unstructured":"Li N, Li L, Wu H, Zhou H. Antioxidative property and molecular mechanisms underlying geniposide-mediated therapeutic effects in diabetes mellitus and cardiovascular disease. Oxid Med Cell Longev. 2019;2019:7480512.","journal-title":"Oxid Med Cell Longev."},{"key":"486_CR13","first-page":"1","volume":"34","author":"Z Chen","year":"2020","unstructured":"Chen Z, Liu W, Qin Z, Liang X, Tian G. Geniposide exhibits anticancer activity to medulloblastoma cells by downregulating microRNA-373. J Biochem Mol Toxicol. 2020;34:1\u201311.","journal-title":"J Biochem Mol Toxicol"},{"key":"486_CR14","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.nrl.2017.02.005","volume":"33","author":"G Lubrini","year":"2018","unstructured":"Lubrini G, Mart\u00edn-Montes A, D\u00edez-Ascaso O, D\u00edez-Tejedor E. Brain disease, connectivity, plasticity and cognitive therapy: a neurological view of mental disorders. Neurologia SEGO. 2018;33:187\u201391.","journal-title":"Neurologia SEGO"},{"key":"486_CR15","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/S0195-5616(96)50113-0","volume":"26","author":"PA March","year":"1996","unstructured":"March PA. Degenerative brain disease. Vet Clin North Am Small Anim Pract. 1996;26:945\u201371.","journal-title":"Vet Clin North Am Small Anim Pract."},{"key":"486_CR16","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1111\/j.1749-6632.2012.06482.x","volume":"1254","author":"JC Kovacic","year":"2012","unstructured":"Kovacic JC, Castellano JM, Fuster V. The links between complex coronary disease, cerebrovascular disease, and degenerative brain disease. Ann N Y Acad Sci. 2012;1254:99\u2013105.","journal-title":"Ann N Y Acad Sci"},{"key":"486_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1176\/ajp.135.1.1","volume":"135","author":"CE Wells","year":"1978","unstructured":"Wells CE. Chronic brain disease: an overview. Am J Psychiatry. 1978;135:1\u201312.","journal-title":"Am J Psychiatry"},{"key":"486_CR18","first-page":"393","volume":"100","author":"OA Sveinsson","year":"2014","unstructured":"Sveinsson OA, Kjartansson O, Valdimarsson EM. Cerebral ischemia\/infarction-diagnosis and treatment. Laeknabladid. 2014;100:393\u2013401.","journal-title":"Laeknabladid."},{"key":"486_CR19","first-page":"271","volume":"100","author":"OA Sveinsson","year":"2014","unstructured":"Sveinsson OA, Kjartansson O, Valdimarsson EM. Cerebral ischemia\/infarction-epidemiology, causes and symptoms. Laeknabladid. 2014;100:271\u20139.","journal-title":"Laeknabladid"},{"key":"486_CR20","first-page":"513","volume":"45","author":"M Wang","year":"2020","unstructured":"Wang M, Liu JX, Yao MJ, Ren JG. Advances in research on pharmacological and neuroprotective effects of traditional Chinese medicine after cerebral ischemia. Zhongguo Zhongyao Zazhi Zhongguo Zhongyi Yanjiuyuan. 2020;45:513\u20137.","journal-title":"Zhongguo Zhongyao Zazhi. Zhongguo Zhongyi Yanjiuyuan"},{"key":"486_CR21","first-page":"733","volume":"4","author":"AN Hasso","year":"1994","unstructured":"Hasso AN, Stringer WA, Brown KD. Cerebral ischemia and infarction. Neuroimaging Clin. 1994;4:733\u201352.","journal-title":"Neuroimaging Clin."},{"key":"486_CR22","first-page":"1","volume":"5","author":"PD Lyden","year":"1993","unstructured":"Lyden PD, Zivin JA. Hemorrhagic transformation after cerebral ischemia: mechanisms and incidence. Cerebrovasc Brain Metab Rev. 1993;5:1\u201316.","journal-title":"Cerebrovasc Brain Metab Rev."},{"key":"486_CR23","first-page":"1027","volume":"45","author":"J Li","year":"2020","unstructured":"Li J, Xu J, Liu Z, Zou Z, Jin M, Tao T. HIF-1\u03b1 attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia-reperfusion injury in a rat MCAO model. Int J Mol Med. 2020;45:1027\u201336.","journal-title":"Int J Mol Med."},{"key":"486_CR24","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1111\/jphp.13294","volume":"72","author":"Y Jiang","year":"2020","unstructured":"Jiang Y, Wen J, Zhang W, Ma Z, Zhang C, Wang J, et al. Metabolomics coupled with integrative pharmacology reveals the therapeutic effect of l-borneolum against cerebral ischaemia in rats. J Pharm Pharmacol. 2020;72:1256\u201368.","journal-title":"J Pharm Pharmacol."},{"key":"486_CR25","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1017\/S135561771700100X","volume":"23","author":"MW Bondi","year":"2017","unstructured":"Bondi MW, Edmonds EC, Salmon DP. Alzheimer\u2019s disease: past, present, and future. J Int Neuropsychol Soc. 2017;23:818\u201331.","journal-title":"J Int Neuropsychol Soc."},{"key":"486_CR26","first-page":"393","volume":"37","author":"C Harr\u00ecson","year":"2008","unstructured":"Harr\u00ecson C, Charles J, Britt H. AD(H)D. Aust Fam Physician. 2008;37:393.","journal-title":"Aust Fam Physician."},{"key":"486_CR27","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/1471-244X-14-107","volume":"14","author":"J Sarris","year":"2014","unstructured":"Sarris J, O\u2019Neil A, Coulson CE, Schweitzer I, Berk M. Lifestyle medicine for depression. BMC Psychiatry. 2014;14:107.","journal-title":"BMC Psychiatry."},{"key":"486_CR28","first-page":"770","volume":"29","author":"M Rai\u010d","year":"2017","unstructured":"Rai\u010d M. Depression and heart diseases: leading health problems. Psychiatr Danub. 2017;29:770\u20137.","journal-title":"Psychiatr Danub."},{"key":"486_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jocn.2017.09.022","volume":"47","author":"Y Zhang","year":"2018","unstructured":"Zhang Y, Chen Y, Ma L. Depression and cardiovascular disease in elderly: current understanding. J Clin Neurosci. 2018;47:1\u20135.","journal-title":"J Clin Neurosci"},{"key":"486_CR30","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/978-1-4939-7526-6_9","volume":"1717","author":"MS Lopez","year":"2018","unstructured":"Lopez MS, Vemuganti R. Modeling transient focal ischemic stroke in rodents by intraluminal filament method of middle cerebral artery occlusion. Methods Mol Biol. 2018;1717:101\u201313.","journal-title":"Methods Mol Biol"},{"key":"486_CR31","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.apsb.2019.11.003","volume":"10","author":"C Xiang","year":"2020","unstructured":"Xiang C, Zhang Y, Guo W, Liang XJ. Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication. Acta Pharm Sin B. 2020;10:239\u201348.","journal-title":"Acta Pharm Sin B."},{"key":"486_CR32","first-page":"464701","volume":"2011","author":"LD McCullough","year":"2011","unstructured":"McCullough LD, Liu F. Middle cerebral artery occlusion model in rodents: methods and potential pitfalls. J Biomed Biotechnol. 2011;2011:464701.","journal-title":"J Biomed Biotechnol."},{"key":"486_CR33","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.apsb.2014.11.002","volume":"5","author":"K Sun","year":"2015","unstructured":"Sun K, Fan J, Han J. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia\/reperfusion-induced cerebral microcirculatory disturbances and neuron damage. Acta Pharm Sin B. 2015;5:8\u201324.","journal-title":"Acta Pharm Sin B"},{"key":"486_CR34","first-page":"3445","volume":"9","author":"F Fluri","year":"2015","unstructured":"Fluri F, Schuhmann MK, Kleinschnitz C. Animal models of ischemic stroke and their application in clinical research. Drug Des Devel Ther. 2015;9:3445\u201354.","journal-title":"Drug Des Devel Ther"},{"key":"486_CR35","doi-asserted-by":"publisher","first-page":"110686","DOI":"10.1016\/j.biopha.2020.110686","volume":"131","author":"R Ma","year":"2020","unstructured":"Ma R, Xie Q, Li Y, Chen Z, Ren M, Chen H, et al. Animal models of cerebral ischemia: a review. Biomed Pharmacother. 2020;131:110686.","journal-title":"Biomed Pharmacother."},{"key":"486_CR36","first-page":"113","volume":"7","author":"T Kalogeris","year":"2017","unstructured":"Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Ischemia\/reperfusion. Compr Physiol. 2017;7:113\u201370.","journal-title":"Compr Physiol"},{"key":"486_CR37","first-page":"1411","volume":"84","author":"A Galkin","year":"2019","unstructured":"Galkin A. Brain Ischemia\/reperfusion injury and mitochondrial complex I damage. Biochem. 2019;84:1411\u201323.","journal-title":"Biochem"},{"key":"486_CR38","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/978-1-4939-7526-6_18","volume":"1717","author":"M Ryou","year":"2018","unstructured":"Ryou M, Mallet RT. An in vitro oxygen\u2013glucose deprivation model for studying ischemia\u2013reperfusion injury of neuronal cells. Methods Mol Biol. 2018;1717:229\u201335.","journal-title":"Methods Mol Biol."},{"key":"486_CR39","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1196\/annals.1344.008","volume":"1053","author":"R Tabakman","year":"2005","unstructured":"Tabakman R, Jiang H, Shahar I, Arien-Zakay H, Levine RA, Lazarovici P. Neuroprotection by NGF in the PC12 in vitro OGD model: Involvement of mitogen-activated protein kinases and gene expression. Ann N Y Acad Sci. 2005;1053:84\u201396.","journal-title":"Ann N Y Acad Sci."},{"key":"486_CR40","first-page":"219","volume":"1717","author":"E Salvador","year":"2018","unstructured":"Salvador E, Burek M, F\u00f6rster CY. An In Vitro Model of Traumatic Brain Injury. Galdos Meow. 2018;1717:219\u201327.","journal-title":"Galdos Meow."},{"key":"486_CR41","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1159\/000480657","volume":"43","author":"B Huang","year":"2017","unstructured":"Huang B, Chen P, Huang L, Li S, Zhu R, Sheng T, et al. Geniposide attenuates post-ischaemic neurovascular damage via GluN2A\/AKT\/ ERK-dependent mechanism. Cell Physiol Biochem. 2017;43:705\u201316.","journal-title":"Cell Physiol Biochem"},{"key":"486_CR42","first-page":"480","volume":"51","author":"LJ Li","year":"2020","unstructured":"Li LJ, Han ZF, Li LX, Yan B. Effects of geniposide on the neuroinflammation in chronic cerebral hypoperfusion rat model. J Sichuan Univ. 2020;51:480\u20137.","journal-title":"J Sichuan Univ."},{"key":"486_CR43","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1007\/s11064-012-0852-8","volume":"37","author":"J Wang","year":"2012","unstructured":"Wang J, Hou J, Zhang P, Li D, Zhang C, Liu J. Geniposide reduces inflammatory responses of oxygen-glucose deprived rat microglial cells via inhibition of the TLR4 signaling pathway. Neurochem Res. 2012;37:2235\u201348.","journal-title":"Neurochem Res"},{"key":"486_CR44","doi-asserted-by":"crossref","first-page":"030006051989385","DOI":"10.1177\/0300060519893859","volume":"48","author":"W Wu","year":"2020","unstructured":"Wu W, He X, Xie S, Li B, Chen J, Qu Y, et al. Protective effects of Huang-Lian-Jie-Du-Tang against A\u03b225\u201335-induced memory deficits and oxidative stress in rats. J Int Med Res. 2020;48:0300060519893859.","journal-title":"J Int Med Res."},{"key":"486_CR45","doi-asserted-by":"publisher","first-page":"111170","DOI":"10.1016\/j.biopha.2020.111170","volume":"134","author":"IJ Lee","year":"2021","unstructured":"Lee IJ, Chao CY, Yang YC, Cheng JJ, Huang CL, Chiou CT, et al. Huang Lian Jie Du Tang attenuates paraquat-induced mitophagy in human SH-SY5Y cells: a traditional decoction with a novel therapeutic potential in treating Parkinson\u2019s disease. Biomed Pharmacother. 2021;134:111170.","journal-title":"Biomed Pharmacother."},{"key":"486_CR46","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1142\/S0192415X14500268","volume":"42","author":"L Pan","year":"2014","unstructured":"Pan L, Zhou J, Zhu H, Wang W, Zhang M, Tian X, et al. Study on integrated pharmacokinetics of gardenia acid and geniposide: time-antioxidant efficacy after oral administration of huanglian-zhizi couplet medicine from huang-lian-jie-du-tang in MCAO rats. Am J Chin Med. 2014;42:393\u2013407.","journal-title":"Am J Chin Med"},{"key":"486_CR47","doi-asserted-by":"crossref","unstructured":"Pan L, Wang W, Shi F, Zhou J, Zhang M, Zhu H, et al. Exploratory pharmacokinetics of geniposide in rat model of cerebral ischemia orally administered with or without baicalin and\/or berberine. Evid Based Complement Altern Med. 2013;2013.","DOI":"10.1155\/2013\/349531"},{"key":"486_CR48","doi-asserted-by":"publisher","first-page":"9848594","DOI":"10.1155\/2017\/9848594","volume":"2017","author":"Q Zhang","year":"2017","unstructured":"Zhang Q, Fu X, Wang J, Yang M, Kong L. Treatment effects of ischemic stroke by berberine, baicalin, and jasminoidin from Huang-Lian-Jie-Du-Decoction (HLJDD) explored by an integrated metabolomics approach. Oxid Med Cell Longev. 2017;2017:9848594.","journal-title":"Oxid Med Cell Longev."},{"key":"486_CR49","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.ejphar.2019.04.021","volume":"854","author":"C Li","year":"2019","unstructured":"Li C, Wang X, Cheng F, Du X, Yan J, Zhai C, et al. Geniposide protects against hypoxia\/reperfusion-induced blood-brain barrier impairment by increasing tight junction protein expression and decreasing inflammation, oxidative stress, and apoptosis in an in vitro system. Eur J Pharmacol. 2019;854:224\u201331.","journal-title":"Eur J Pharmacol."},{"key":"486_CR50","doi-asserted-by":"publisher","first-page":"106609","DOI":"10.1016\/j.intimp.2020.106609","volume":"85","author":"X Luo","year":"2020","unstructured":"Luo X, Wu S, Jiang Y, Wang L, Li G, Qing Y, et al. Inhibition of autophagy by geniposide protects against myocardial ischemia\/reperfusion injury. Int Immunopharmacol. 2020;85:106609.","journal-title":"Int Immunopharmacol."},{"key":"486_CR51","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.cell.2019.08.053","volume":"179","author":"M Prinz","year":"2019","unstructured":"Prinz M, Jung S, Priller J. Microglia biology: one century of evolving concepts. Cell. 2019;179:292\u2013311.","journal-title":"Cell."},{"key":"486_CR52","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1146\/annurev-physiol-022516-034406","volume":"79","author":"SA Wolf","year":"2017","unstructured":"Wolf SA, Boddeke HWGM, Kettenmann H. Microglia in physiology and disease. Annu Rev Physiol. 2017;79:619\u201343.","journal-title":"Annu Rev Physiol"},{"key":"486_CR53","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1146\/annurev-immunol-032713-120240","volume":"32","author":"D Nayak","year":"2014","unstructured":"Nayak D, Roth TL, McGavern DB. Microglia development and function. Annu Rev Immunol. 2014;32:367\u2013402.","journal-title":"Annu Rev Immunol"},{"key":"486_CR54","doi-asserted-by":"publisher","first-page":"106547","DOI":"10.1016\/j.intimp.2020.106547","volume":"84","author":"C Fu","year":"2020","unstructured":"Fu C, Zhang X, Lu Y, Wang F, Xu Z, Liu S, et al. Geniposide inhibits NLRP3 inflammasome activation via autophagy in BV-2 microglial cells exposed to oxygen\u2013glucose deprivation\/reoxygenation. Int Immunopharmacol. 2020;84:106547.","journal-title":"Int Immunopharmacol."},{"key":"486_CR55","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1038\/s41401-019-0286-9","volume":"40","author":"X Shen","year":"2019","unstructured":"Shen X, Zhao YF, Xu SQ, Wang L, Cao HM, Cao Y, et al. Cathepsin L induced PC-12 cell apoptosis via activation of B-Myb and regulation of cell cycle proteins. Acta Pharmacol Sin. 2019;40:1394\u2013403.","journal-title":"Acta Pharmacol Sin."},{"key":"486_CR56","doi-asserted-by":"crossref","first-page":"847","DOI":"10.21873\/anticanres.12625","volume":"38","author":"J Jung","year":"2018","unstructured":"Jung J, Jeongbin SEO, Joungmok KIM, Kim JHEE. Ursolic acid causes cell death in PC-12 cells by inducing apoptosis and impairing autophagy. Anticancer Res. 2018;38:847\u201353.","journal-title":"Anticancer Res"},{"key":"486_CR57","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1016\/j.biopha.2018.09.147","volume":"108","author":"R Li","year":"2018","unstructured":"Li R, Yin F, Guo Y, Ruan Q, Zhu Q. Angelica polysaccharide protects PC-12 cells from lipopolysaccharide-induced injury via down-regulating microRNA-223. Biomed Pharmacother. 2018;108:1320\u20137.","journal-title":"Biomed Pharmacother"},{"key":"486_CR58","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.lfs.2018.11.047","volume":"216","author":"Y Yuan","year":"2019","unstructured":"Yuan Y, Zheng Z. Geniposide protects PC-12 cells against oxygen and glucose deprivation-induced injury by up-regulation of long-noncoding RNA H19. Life Sci. 2019;216:176\u201382.","journal-title":"Life Sci"},{"key":"486_CR59","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jep.2016.03.025","volume":"185","author":"F Li","year":"2016","unstructured":"Li F, Li W, Li X, Li F, Zhang L, Wang B, et al. Geniposide attenuates inflammatory response by suppressing P2Y14 receptor and downstream ERK1\/2 signaling pathway in oxygen and glucose deprivation-induced brain microvascular endothelial cells. J Ethnopharmacol. 2016;185:77\u201386.","journal-title":"J Ethnopharmacol"},{"key":"486_CR60","doi-asserted-by":"publisher","first-page":"172484","DOI":"10.1016\/j.ejphar.2019.172484","volume":"859","author":"J Wu","year":"2019","unstructured":"Wu J, Wang B, Li M, Shi YH, Wang C, Kang YG. Network pharmacology identification of mechanisms of cerebral ischemia injury amelioration by Baicalin and Geniposide. Eur J Pharmacol. 2019;859:172484.","journal-title":"Eur J Pharmacol."},{"key":"486_CR61","first-page":"320","volume":"15","author":"F Cheng","year":"2018","unstructured":"Cheng F, Ma C, Sun L, Zhang X, Zhai C, Li C, et al. Synergistic neuroprotective effects of geniposide and ursodeoxycholic acid in hypoxia-reoxygenation injury in SH-SY5Y cells. Exp Ther Med. 2018;15:320\u20136.","journal-title":"Exp Ther Med"},{"key":"486_CR62","doi-asserted-by":"publisher","first-page":"10242","DOI":"10.18632\/aging.102451","volume":"11","author":"L Chen","year":"2019","unstructured":"Chen L, Xu S, Wu T, Shao Y, Luo L, Zhou L, et al. Studies on APP metabolism related to age-associated mitochondrial dysfunction in APP\/PS1 transgenic mice. Aging. 2019;11:10242\u201351.","journal-title":"Aging"},{"key":"486_CR63","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1080\/00207454.2019.1688808","volume":"130","author":"J Xiang","year":"2020","unstructured":"Xiang J, Cao K, Dong YT, Xu Y, Li Y, Song H, et al. Lithium chloride reduced the level of oxidative stress in brains and serums of APP\/PS1 double transgenic mice via the regulation of GSK3\u03b2\/Nrf2\/HO-1 pathway. Int J Neurosci. 2020;130:564\u201373.","journal-title":"Int J Neurosci"},{"key":"486_CR64","doi-asserted-by":"publisher","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","volume":"26","author":"H Oakley","year":"2006","unstructured":"Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, et al. Intraneuronal \u03b2-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer\u2019s disease mutations: potential factors in amyloid plaque formation. J Neurosci. 2006;26:10129\u201340.","journal-title":"J Neurosci"},{"key":"486_CR65","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1007\/s00125-007-0886-7","volume":"51","author":"S Lenzen","year":"2008","unstructured":"Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008;51:216\u201326.","journal-title":"Diabetologia"},{"key":"486_CR66","first-page":"1741","volume":"53","author":"P Grieb","year":"2016","unstructured":"Grieb P. Intracerebroventricular streptozotocin injections as a model of Alzheimer\u2019s disease: in search of a relevant mechanism. Neurobiol. 2016;53:1741\u201352.","journal-title":"Neurobiol."},{"key":"486_CR67","doi-asserted-by":"publisher","first-page":"26","DOI":"10.2174\/1573399815666190411115829","volume":"16","author":"MA Baig","year":"2019","unstructured":"Baig MA, Panchal SS. Streptozotocin-induced diabetes mellitus in neonatal rats: an insight into its applications to induce diabetic complications. Curr Diabetes Rev. 2019;16:26\u201339.","journal-title":"Curr Diabetes Rev"},{"key":"486_CR68","doi-asserted-by":"publisher","first-page":"536","DOI":"10.18632\/aging.101759","volume":"11","author":"Z Zhang","year":"2019","unstructured":"Zhang Z, Wang X, Zhang D, Liu Y, Li L. Geniposide-mediated protection against amyloid deposition and behavioral impairment correlates with downregulation of mTOR signaling and enhanced autophagy in a mouse model of Alzheimer\u2019s disease. Aging. 2019;11:536\u201348.","journal-title":"Aging"},{"key":"486_CR69","doi-asserted-by":"publisher","first-page":"134749","DOI":"10.1016\/j.neulet.2020.134749","volume":"720","author":"Z Zhang","year":"2020","unstructured":"Zhang Z, Gao W, Wang X, Zhang D, Liu YZ, Li L. Geniposide effectively reverses cognitive impairment and inhibits pathological cerebral damage by regulating the mTOR Signal pathway in APP\u2215PS1 mice. Neurosci Lett. 2020;720:134749.","journal-title":"Neurosci Lett."},{"key":"486_CR70","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1111\/cbdd.12673","volume":"87","author":"Y Zhang","year":"2016","unstructured":"Zhang Y, Yin F, Liu J, Liu Z. Geniposide attenuates the phosphorylation of tau protein in cellular and insulin-deficient APP\/PS1 transgenic mouse model of Alzheimer\u2019s disease. Chem Biol Drug Des. 2016;87:409\u201318.","journal-title":"Chem Biol Drug Des"},{"key":"486_CR71","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neuropharm.2016.12.002","volume":"116","author":"C Zhao","year":"2017","unstructured":"Zhao C, Zhang H, Li H, Lv C, Liu X, Li Z, et al. Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice. Neuropharmacology. 2017;116:18\u201329.","journal-title":"Neuropharmacology"},{"key":"486_CR72","doi-asserted-by":"publisher","first-page":"580","DOI":"10.2174\/1567205011666140618095925","volume":"11","author":"C Lv","year":"2014","unstructured":"Lv C, Liu X, Liu H, Chen T, Zhang W. Geniposide attenuates mitochondrial dysfunction and memory deficits in APP\/PS1 transgenic mice. Curr Alzheimer Res. 2014;11:580\u20137.","journal-title":"Curr Alzheimer Res."},{"key":"486_CR73","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.neuint.2015.04.002","volume":"89","author":"Y Zhang","year":"2015","unstructured":"Zhang Y, Yin F, Liu J, Liu Z, Guo L, Xia Z, et al. Geniposide attenuates insulin-deficiency-induced acceleration of \u03b2-amyloidosis in an APP\/PS1 transgenic model of Alzheimer\u2019s disease. Neurochem Int. 2015;89:7\u201316.","journal-title":"Neurochem Int"},{"key":"486_CR74","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1111\/bpa.12116","volume":"24","author":"C Gao","year":"2014","unstructured":"Gao C, Liu Y, Jiang Y, Ding J, Li L. Geniposide ameliorates learning memory deficits, reduces tau phosphorylation and decreases apoptosis via GSK3\u03b2 Pathway in streptozotocin-induced alzheimer rat model. Brain Pathol. 2014;24:261\u20139.","journal-title":"Brain Pathol"},{"key":"486_CR75","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1093\/abbs\/gmt069","volume":"45","author":"J Liu","year":"2013","unstructured":"Liu J, Zhang Y, Deng X, Yin F. Geniposide decreases the level of A\u03b21-42 in the hippocampus of streptozotocin-induced diabetic rats. Acta Biochim Biophys Sin. 2013;45:787\u201391.","journal-title":"Acta Biochim Biophys Sin"},{"key":"486_CR76","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1007\/s11064-018-2469-z","volume":"43","author":"H Cui","year":"2018","unstructured":"Cui H, Deng M, Zhang Y, Yin F, Liu J. Geniposide increases unfolded protein response-mediating HRD1 expression to accelerate APP degradation in primary cortical neurons. Neurochem Res. 2018;43:669\u201380.","journal-title":"Neurochem Res."},{"key":"486_CR77","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1093\/abbs\/gmv106","volume":"47","author":"J Liu","year":"2015","unstructured":"Liu J, Liu Z, Zhang Y, Yin F. Leptin signaling plays a critical role in the geniposide-induced decrease of tau phosphorylation. Acta Biochim Biophys Sin. 2015;47:1018\u201322.","journal-title":"Acta Biochim Biophys Sin"},{"key":"486_CR78","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1007\/s12272-016-0875-9","volume":"40","author":"Z Liu","year":"2017","unstructured":"Liu Z, Zhang Y, Liu J, Yin F. Geniposide attenuates the level of A\u03b21\u201342 via enhancing leptin signaling in cellular and APP\/PS1 transgenic mice. Arch Pharm Res. 2017;40:571\u20138.","journal-title":"Arch Pharm Res."},{"key":"486_CR79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12915-020-00927-9","volume":"19","author":"AC Arcones","year":"2021","unstructured":"Arcones AC, Vila-Bedmar R, Mirasierra M, Cruces-Sande M, Vallejo M, Jones B, et al. GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo. BMC Biol BMC Biol. 2021;19:1\u201316.","journal-title":"BMC Biol BMC Biol"},{"key":"486_CR80","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/bs.apha.2020.02.001","volume":"88","author":"FS Willard","year":"2020","unstructured":"Willard FS, Ho JD, Sloop KW. Discovery and pharmacology of the covalent GLP-1 receptor (GLP-1R) allosteric modulator BETP: a novel tool to probe GLP-1R pharmacology. Adv Pharmacol. 2020;88:173\u201391.","journal-title":"Adv Pharmacol."},{"key":"486_CR81","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/j.cmet.2018.03.001","volume":"27","author":"DJ Drucker","year":"2018","unstructured":"Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27:740\u201356.","journal-title":"Cell Metab."},{"key":"486_CR82","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1080\/14656566.2018.1519547","volume":"19","author":"SA Doggrell","year":"2018","unstructured":"Doggrell SA. Do glucagon-like peptide-1 receptor (GLP-1R) agonists have potential as adjuncts in the treatment of type 1 diabetes? Expert Opin Pharmacother. 2018;19:1655\u201361.","journal-title":"Expert Opin. Pharmacother."},{"key":"486_CR83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-03941-2","volume":"9","author":"B Jones","year":"2018","unstructured":"Jones B, Buenaventura T, Kanda N, Chabosseau P, Owen BM, Scott R, et al. Targeting GLP-1 receptor trafficking to improve agonist efficacy. Nat Commun. 2018;9:1\u20137.","journal-title":"Nat Commun."},{"issue":"7","key":"486_CR84","doi-asserted-by":"publisher","first-page":"2911","DOI":"10.1007\/s10072-020-04910-8","volume":"42","author":"TS Trammell","year":"2020","unstructured":"Trammell TS, Henderson NL, Madkour HS, Stanwood GD, Graham DL. GLP-1R activation alters performance in cognitive tasks in a sex-dependent manner. Neurol Sci. 2020;42(7):2911\u20139.","journal-title":"Neurol Sci."},{"key":"486_CR85","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1515\/revneuro-2015-0005","volume":"26","author":"W Liu","year":"2015","unstructured":"Liu W, Li G, H\u00f6lscher C, Li L. Neuroprotective effects of geniposide on Alzheimer\u2019s disease pathology. Rev Neurosci. 2015;26:371\u201383.","journal-title":"Rev Neurosci"},{"key":"486_CR86","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/aps.2008.25","volume":"30","author":"JH Liu","year":"2009","unstructured":"Liu JH, Yin F, Guo LX, Deng XH, Hu YH. Neuroprotection of geniposide against hydrogen peroxide induced PC12 cells injury: involvement of PI3 kinase signal pathway. Acta Pharmacol Sin. 2009;30:159\u201365.","journal-title":"Acta Pharmacol Sin"},{"key":"486_CR87","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.neuint.2007.04.021","volume":"51","author":"J Liu","year":"2007","unstructured":"Liu J, Yin F, Zheng X, Jing J, Hu Y. Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway. Neurochem Int. 2007;51:361\u20139.","journal-title":"Neurochem Int"},{"key":"486_CR88","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.neubiorev.2018.12.002","volume":"99","author":"S Antoniuk","year":"2019","unstructured":"Antoniuk S, Bijata M, Ponimaskin E, Wlodarczyk J. Chronic unpredictable mild stress for modeling depression in rodents: meta-analysis of model reliability. Neurosci Biobehav Rev Elsevier Ltd. 2019;99:101\u201316.","journal-title":"Neurosci Biobehav Rev Elsevier Ltd"},{"key":"486_CR89","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1038\/mp.2017.130","volume":"23","author":"L Colodro-Conde","year":"2018","unstructured":"Colodro-Conde L, Couvy-Duchesne B, Zhu G, Coventry WL, Byrne EM, Gordon S, et al. A direct test of the diathesis\u2013stress model for depression. Mol Psychiatry. 2018;23:1590\u20136.","journal-title":"Mol Psychiatry"},{"key":"486_CR90","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s11033-019-05129-3","volume":"47","author":"E Pitsillou","year":"2020","unstructured":"Pitsillou E, Bresnehan SM, Kagarakis EA, Wijoyo SJ, Liang J, Hung A, et al. The cellular and molecular basis of major depressive disorder: towards a unified model for understanding clinical depression. Mol Biol Rep. 2020;47:753\u201370.","journal-title":"Mol Biol Rep."},{"key":"486_CR91","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.neulet.2018.04.010","volume":"676","author":"Y Zhao","year":"2018","unstructured":"Zhao Y, Li H, Fang F, Qin T, Xiao W, Wang Z, et al. Geniposide improves repeated restraint stress-induced depression-like behavior in mice by ameliorating neuronal apoptosis via regulating GLP-1R\/AKT signaling pathway. Neurosci Lett. 2018;676:19\u201326.","journal-title":"Neurosci Lett"},{"key":"486_CR92","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.euroneuro.2015.04.009","volume":"25","author":"L Cai","year":"2015","unstructured":"Cai L, Li R, Tang WJ, Meng G, Hu XY, Wu TN. Antidepressant-like effect of geniposide on chronic unpredictable mild stress-induced depressive rats by regulating the hypothalamus-pituitary-adrenal axis. Eur Neuropsychopharmacol. 2015;25:1332\u201341.","journal-title":"Eur Neuropsychopharmacol"},{"key":"486_CR93","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1007\/s11011-016-9856-4","volume":"31","author":"J Wang","year":"2016","unstructured":"Wang J, Duan P, Cui Y, Li Q, Shi Y. Geniposide alleviates depression-like behavior via enhancing BDNF expression in hippocampus of streptozotocin-evoked mice. Metab Brain Dis Metabolic Brain Disease. 2016;31:1113\u201322.","journal-title":"Metab Brain Dis Metabolic Brain Disease"},{"key":"486_CR94","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.neures.2020.05.003","volume":"165","author":"B Sun","year":"2020","unstructured":"Sun B, Jia X, Yang F, Ren G, Wu X. CREB-mediated generation and neuronal growth regulates the behavioral improvement of geniposide in diabetes-associated depression mouse model. Neurosci Res. 2020;165:38\u201344.","journal-title":"Neurosci Res."},{"key":"486_CR95","first-page":"1","volume":"27","author":"B Zhang","year":"2019","unstructured":"Zhang B, Chang HS, Hu KL, Yu X, Li LN, Xu XQ. Combination of geniposide and eleutheroside B exerts antidepressant-like effect on lipopolysaccharide-induced depression mice model. Chin J Integr Med. 2019;27:1\u20138.","journal-title":"Chin J Integr Med."},{"key":"486_CR96","first-page":"1136","volume":"15","author":"H Wei","year":"2018","unstructured":"Wei H, Duan G, He J, Meng Q, Liu Y, Chen W, et al. Geniposide attenuates epilepsy symptoms in a mouse model through the PI3K\/Akt\/GSK-3\u03b2 signaling pathway. Exp Ther Med. 2018;15:1136\u201342.","journal-title":"Exp Ther Med"},{"key":"486_CR97","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ejphar.2015.09.029","volume":"768","author":"Y Chen","year":"2015","unstructured":"Chen Y, Zhang Y, Li L, H\u00f6lscher C. Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson\u2019s disease. Eur J Pharmacol. 2015;768:21\u20137.","journal-title":"Eur J Pharmacol"},{"key":"486_CR98","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.brainres.2016.05.011","volume":"1644","author":"C Su","year":"2016","unstructured":"Su C, Yang X, Lou J. Geniposide reduces \u03b1-synuclein by blocking microRNA-21\/lysosome-associated membrane protein 2A interaction in Parkinson disease models. Brain Res. 2016;1644:98\u2013106.","journal-title":"Brain Res"},{"key":"486_CR99","doi-asserted-by":"publisher","first-page":"4925682","DOI":"10.1155\/2019\/4925682","volume":"2019","author":"Y-X Zhou","year":"2019","unstructured":"Zhou Y-X, Zhang R-Q, Rahman K, Cao Z-X, Zhang H, Peng C. Diverse pharmacological activities and potential medicinal benefits of geniposide. Evid Based Complement Alternat Med. 2019;2019:4925682.","journal-title":"Evid Based Complement Alternat Med"},{"key":"486_CR100","first-page":"1499","volume":"20","author":"T He","year":"2019","unstructured":"He T, Shen H, Zhu J, Zhu Y, He Y, Li Z, et al. Geniposide attenuates cadmium-induced oxidative stress injury via Nrf2 signaling in osteoblasts. Mol Med Rep. 2019;20:1499\u2013508.","journal-title":"Mol Med Rep"},{"key":"486_CR101","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.7150\/ijms.51329","volume":"17","author":"L Hu","year":"2020","unstructured":"Hu L, Zhao J, Liu Y, Liu X, Lu Q, Zeng Z, et al. Geniposide inhibits proliferation and induces apoptosis of diffuse large B-cell lymphoma cells by inactivating the HCP5\/miR-27b-3p\/MET axis. Int J Med Sci. 2020;17:2735\u201343.","journal-title":"Int J Med Sci"},{"key":"486_CR102","doi-asserted-by":"publisher","first-page":"2875","DOI":"10.1080\/21691401.2019.1626406","volume":"47","author":"S Ma","year":"2019","unstructured":"Ma S, Zhang C, Zhang Z, Dai Y, Gu R, Jiang R. Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145\u20135p. Artif Cells Nanomed Biotechnol. 2019;47:2875\u201381.","journal-title":"Artif Cells Nanomed Biotechnol."},{"key":"486_CR103","doi-asserted-by":"publisher","first-page":"3240","DOI":"10.1111\/bph.15046","volume":"177","author":"C Zhang","year":"2020","unstructured":"Zhang C, Wang N, Tan HY, Guo W, Chen F, Zhong Z, et al. Direct inhibition of the TLR4\/MyD88 pathway by geniposide suppresses HIF-1\u03b1-independent VEGF expression and angiogenesis in hepatocellular carcinoma. Br J Pharmacol. 2020;177:3240\u201357.","journal-title":"Br J Pharmacol"},{"key":"486_CR104","doi-asserted-by":"publisher","first-page":"4483","DOI":"10.1021\/acs.jafc.9b00402","volume":"67","author":"Y Li","year":"2019","unstructured":"Li Y, Pan H, Zhang X, Wang H, Liu S, Zhang H, et al. Geniposide improves glucose homeostasis via regulating FoxO1\/PDK4 in skeletal muscle. J Agric Food Chem. 2019;67:4483\u201392.","journal-title":"J Agric Food Chem"},{"key":"486_CR105","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s12272-012-0418-y","volume":"35","author":"MJ Kang","year":"2012","unstructured":"Kang MJ, Khanal T, Kim HG, Lee DH, Yeo HK, Lee YS, et al. Role of metabolism by human intestinal microflora in geniposideinduced toxicity in HepG2 cells. Arch Pharm Res. 2012;35:733\u20138.","journal-title":"Arch Pharm Res."},{"key":"486_CR106","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-09131-2","volume":"7","author":"J Tian","year":"2017","unstructured":"Tian J, Zhu J, Yi Y, Li C, Zhang Y, Zhao Y, et al. Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation. Sci Rep. 2017;7:1.","journal-title":"Sci Rep."},{"key":"486_CR107","first-page":"4234","volume":"44","author":"YZ Hu","year":"2019","unstructured":"Hu YZ, Li DF, Zhang Y, Wei JY, Yang HJ. Marker genes of geniposide-induced hepatotoxicity based on genomic strategy. Zhongguo Zhongyao Zazhi Zhongguo Zhongyi Yanjiuyuan. 2019;44:4234\u201340.","journal-title":"Zhongguo Zhongyao Zazhi. Zhongguo Zhongyi Yanjiuyuan"},{"key":"486_CR108","doi-asserted-by":"publisher","first-page":"114624","DOI":"10.1016\/j.taap.2019.114624","volume":"377","author":"Y Li","year":"2019","unstructured":"Li Y, Pan H, Li X, Jiang N, Huang L, Lu Y, et al. Role of intestinal microbiota-mediated genipin dialdehyde intermediate formation in geniposide-induced hepatotoxicity in rats. Toxicol Appl Pharmacol. 2019;377:114624.","journal-title":"Toxicol Appl Pharmacol."},{"key":"486_CR109","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.jep.2017.11.008","volume":"213","author":"J Tian","year":"2018","unstructured":"Tian J, Yi Y, Zhao Y, Li C, Zhang Y, Wang L, et al. Oral chronic toxicity study of geniposide in rats. J Ethnopharmacol. 2018;213:166\u201375.","journal-title":"J Ethnopharmacol"},{"key":"486_CR110","doi-asserted-by":"publisher","first-page":"173578","DOI":"10.1016\/j.ejphar.2020.173578","volume":"888","author":"X Ma","year":"2020","unstructured":"Ma X, Jiang Y, Wen J, Zhao Y, Zeng J, Guo Y. A comprehensive review of natural products to fight liver fibrosis: alkaloids, terpenoids, glycosides, coumarins and other compounds. Eur J Pharmacol. 2020;888:173578.","journal-title":"Eur J Pharmacol."},{"key":"486_CR111","doi-asserted-by":"publisher","first-page":"531","DOI":"10.3389\/fphar.2020.00531","volume":"11","author":"X Ma","year":"2020","unstructured":"Ma X, Zhang W, Jiang Y, Wen J, Wei S, Zhao Y, et al. Article 531 1 (2020) paeoniflorin, a natural product with multiple targets in liver diseases-a mini review. Front Pharmacol. 2020;11:531.","journal-title":"Front Pharmacol"},{"key":"486_CR112","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1002\/ptr.6621","volume":"34","author":"X Ma","year":"2020","unstructured":"Ma X, Jiang Y, Zhang W, Wang J, Wang R, Wang L, et al. Natural products for the prevention and treatment of cholestasis: a review. Phyther Res. 2020;34:1291\u2013309.","journal-title":"Phyther Res."}],"container-title":["Chinese Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13020-021-00486-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13020-021-00486-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13020-021-00486-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T23:23:21Z","timestamp":1699399401000},"score":1,"resource":{"primary":{"URL":"https:\/\/cmjournal.biomedcentral.com\/articles\/10.1186\/s13020-021-00486-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,28]]},"references-count":112,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["486"],"URL":"https:\/\/doi.org\/10.1186\/s13020-021-00486-3","relation":{},"ISSN":["1749-8546"],"issn-type":[{"value":"1749-8546","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,28]]},"assertion":[{"value":"13 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not available.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors consent to publish.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"86"}}