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Excessive Angiotensin II (Ang II)\u2013driven inflammation, apoptosis, and fibrosis are central to its pathogenesis. Salvianolic acid A (SAA), a polyphenolic compound from\n                    <jats:italic>Salvia miltiorrhiza<\/jats:italic>\n                    , has anti\u2010inflammatory properties, but its therapeutic potential in HN is unclear. HN was induced in mice by continuous subcutaneous infusion of Ang II (1.44 mg\/kg\/day) for 28 days. SAA (10 or 20 mg\/kg\/day) was administered orally every day during the final 14 days. Network pharmacology suggested SAA targets the TLR4\/PI3K\/AKT\/NF\u2010\u03baB pathway. SAA administration improved renal function and attenuated inflammatory infiltration, tubular cell apoptosis, and interstitial fibrosis, independent of systemic blood pressure. NRK\u201052E cells were used in vitro. SAA inhibited PI3K and AKT phosphorylation, suppressed NF\u2010\u03baB P65 activation, and downregulated pro\u2010inflammatory cytokines. The PI3K activator 740 Y\u2010P abolished these effects. Pull\u2010down, DARTS assays and molecular docking showed interaction between SAA and TLR4, while TLR4 overexpression reversed SAA's protective actions. These findings provide the evidence that SAA exerts protective effects against Ang II\u2010induced HN, acting through inhibition of the TLR4\/MyD88\/PI3K\/AKT\/NF\u2010\u03baB axis and represents a potential TLR4\u2010targeted therapy for hypertensive kidney injury.\n                  <\/jats:p>","DOI":"10.1002\/mnfr.70371","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T14:20:29Z","timestamp":1768573229000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Salvianolic Acid A Protects Against Angiotensin II\u2010Induced Hypertensive Kidney Disease by Targeting TLR4 and Inhibiting TLR4\/Myd88\/PI3K\/AKT\/NF\u2010\u03baB Pathway"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8949-1413","authenticated-orcid":false,"given":"Wenhan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital 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