{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T12:05:38Z","timestamp":1789214738668,"version":"build-2803163510"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The calcium-sensing receptor (CaSR), a G protein-coupled receptor (GPCR), plays a critical role in kidney injury by promoting inflammation and apoptosis when activated. Whether Wulingsan (WLS), a traditional Chinese herbal formula used for kidney disorders, exerts its protective effects against acute kidney injury (AKI) via modulation of the CaSR pathway remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      WLS\u2019s chemical profile was characterized by ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrometry (UHPLC-QE-MS). C57BL\/6J mice were divided into Control, cisplatin (CP)-induced AKI, WLS (2.34\/4.68\/9.36\u00a0g\/kg), and CaSR inhibitor NPS2143 (4.5\u00a0mg\/kg) groups. Mice were pretreated with WLS\/NPS2143 before CP injection (20\u00a0mg\/kg, i. p.). Renal function, histopathology, inflammation, oxidative stress, and apoptosis were evaluated. Cisplatin-induced mouse renal tubular epithelial cells (mRTECs) were treated with WLS-containing serum (5%\u201310%) for\n                      <jats:italic>in vitro<\/jats:italic>\n                      validation. Molecular docking predicted the binding affinity of WLS components to CaSR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      UHPLC-QE-MS identified 15 major WLS components, with 13 binding to CaSR (Polyporusterone E: binding energy of \u221210.4\u00a0kcal\/mol). WLS pretreatment significantly improved renal function (reduced serum creatinine (SCr)\/blood urea nitrogen (BUN)), attenuated tubular injury, suppressed inflammation (downregulated monocyte chemoattractant protein-1 (MCP-1)\/tumor necrosis factor-\u03b1 (TNF-\u03b1)\/interleukin-1\u03b2 (IL-1\u03b2)), alleviated oxidative stress (restored glutathione (GSH)\/superoxide dismutase (SOD), reduced malondialdehyde (MDA)), and inhibited apoptosis (decreased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, modulated Bcl-2-associated X protein (Bax)\/B-cell lymphoma-2 (Bcl-2) ratio, downregulated cleaved Caspase 3). Mechanistically, WLS inhibited renal CaSR\/calmodulin-dependent protein kinase \u03b2 (CaMKK\u03b2)\/adenosine 5\u2032-monophosphate (AMP)-activated protein kinase (AMPK) pathway activation (reduced CaSR\/CaMKK\u03b2\/p-AMPK expression).\n                      <jats:italic>In vitro<\/jats:italic>\n                      , WLS-containing serum reduced cisplatin-induced reactive oxygen species (ROS) production, intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      overload, and apoptosis in mRTECs, effects reversed by the CaSR agonist cinacalcet.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that WLS protects against CP-induced kidney injury and inhibits apoptosis in renal tubular epithelial cells in association with the CaSR\/CaMKK\u03b2\/AMPK pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1824226","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T10:25:42Z","timestamp":1782469542000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Wulingsan alleviates cisplatin-induced acute kidney injury and inhibits renal tubular epithelial cell apoptosis in association with the CaSR\/CaMKK\u03b2\/AMPK pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiuye","family":"Huang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxian","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongan","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xipan","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengliang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Affiliated Gaozhou People\u2019s Hospital, Guangdong Medical University","place":["Gaozhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuyao","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101007","DOI":"10.1016\/j.imr.2023.101007","article-title":"Herbal medicine (oryeongsan) for fluid and sodium balance in renal cortex of spontaneously hypertensive rats","volume":"13","author":"Ahn","year":"2024","journal-title":"Integr. 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