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Recent epidemiological studies suggest that echinacoside (ECH), a phenylethanoid glycoside found in <jats:italic>Cistanche deserticola<\/jats:italic>, has a protective effect against the development of PD. However, the detailed mechanisms of how ECH suppresses neuronal death have not been fully elucidated. In this study, we confirmed that ECH protects nigrostriatal neurons against 6\u2010hydroxydopamine (6\u2010OHDA)\u2010induced endoplasmic reticulum stress (ERS) <jats:italic>in\u00a0vivo<\/jats:italic> and <jats:italic>in\u00a0vitro<\/jats:italic>. ECH rescued cell viability in damaged cells and decreased 6\u2010OHDA\u2010induced reactive oxygen species accumulation <jats:italic>in\u00a0vitro<\/jats:italic>. It also rescued tyrosine hydroxylase and dopamine transporter expression in the striatum, and decreased \u03b1\u2010synuclein aggregation following 6\u2010OHDA treatment <jats:italic>in\u00a0vivo<\/jats:italic>. The validated mechanism of ECH activity was the reduction in the 6\u2010OHDA\u2010induced accumulation of seipin (Berardinelli\u2013Seip congenital lipodystrophy 2). Seipin has been shown to be a key molecule related to motor neuron disease and was tightly associated with ERS in a series of <jats:italic>in\u00a0vivo<\/jats:italic> studies. ECH attenuated seipinopathy by promoting seipin degradation <jats:italic>via<\/jats:italic> ubiquitination. ERS was relieved by ECH through the Grp94\/Bip\u2010ATF4\u2010CHOP signal pathway.<\/jats:p>","DOI":"10.1111\/jcmm.13285","type":"journal-article","created":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T12:52:42Z","timestamp":1501678362000},"page":"3761-3775","source":"Crossref","is-referenced-by-count":35,"title":["Echinacoside's nigrostriatal dopaminergic protection against 6\u2010OHDA\u2010Induced endoplasmic reticulum stress through reducing the accumulation of Seipin"],"prefix":"10.1111","volume":"21","author":[{"given":"Yajie","family":"Zhang","sequence":"first","affiliation":[{"name":"Central Laboratory The Third Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing Jiangsu China"},{"name":"Clinical Biobank of Nanjing Hospital of Chinese Medicine The Third Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Long","sequence":"additional","affiliation":[{"name":"Central Laboratory The Third Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing Jiangsu China"},{"name":"Clinical Biobank of Nanjing Hospital of Chinese Medicine The Third Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing Jiangsu China"},{"name":"Department of Pediatrics The Third Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuqiong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of T.C.M. 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