{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:30:34Z","timestamp":1783002634909,"version":"3.54.5"},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2011,3,22]],"date-time":"2011-03-22T00:00:00Z","timestamp":1300752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> The combination of Chinese herbs, Astragali Radix and Angelicae Sinensis Radix, could alleviate renal interstitial fibrosis. Astragaloside IV (AS\u2010IV) and ferulic acid (FA) are the two major active constituents in this combination. In this study, we employed rats with unilateral ureteral obstruction to determine whether AS\u2010IV and FA have the same renoprotective effects and investigated the mechanisms of this action.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> Renal pathological changes were evaluated after treatment with AS\u2010IV, FA or AS\u2010IV + FA (<jats:italic>AF<\/jats:italic>) for 10 days. Meanwhile, the expression of transforming growth factor \u03b2<jats:sub>1<\/jats:sub> (TGF\u2010\u03b2<jats:sub>1<\/jats:sub>), fibronectin, \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), phosphorylation of c\u2010Jun NH<jats:sub>2<\/jats:sub>\u2010terminal kinase (p\u2010JNK) and nitric oxide (NO) production in kidney were determined. The expressions of fibronectin, \u03b1\u2010SMA, mitogen\u2010activated protein kinases [JNK, extracellular signal\u2010regulated kinases (ERK), P38] in TGF\u2010\u03b2<jats:sub>1<\/jats:sub>\u2010treated NRK\u201049F cells or interleukin\u20101\u2010treated HK\u20102 cells after AS\u2010IV, FA or <jats:italic>AF<\/jats:italic> were assessed.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>  <jats:italic>AF<\/jats:italic> alleviated the infiltration of mononuclear cells, tubular atrophy and interstitial fibrosis; reduced the expression of fibronectin, \u03b1\u2010SMA, TGF\u2010\u03b2<jats:sub>1<\/jats:sub> and p\u2010JNK; and dramatically increased the production of NO in obstructed kidneys. Neither AS\u2010IV nor FA alone improved renal damage, but both increased NO production. <jats:italic>AF<\/jats:italic> inhibited \u03b1\u2010SMA and fibronectin expression in NRK\u201049F or HK\u20102 cells. Furthermore, <jats:italic>AF<\/jats:italic> significantly inhibited IL\u20101\u03b2\u2010induced JNK phosphorylation, without affecting ERK or P38 phosphorylation. Neither AS\u2010IV nor FA alone had any effect on the cells.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> AS\u2010IV synergizes with FA to alleviate renal tubulointerstitial fibrosis; this was associated with inhibition of tubular epithelial\u2013mesenchymal transdifferentiation (EMT) and fibroblast activation, as well as an increase in NO production in the kidney.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01206.x","type":"journal-article","created":{"date-parts":[[2011,1,14]],"date-time":"2011-01-14T12:25:31Z","timestamp":1295007931000},"page":"1805-1818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Astragaloside IV synergizes with ferulic acid to inhibit renal tubulointerstitial fibrosis in rats with obstructive 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