{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:06:16Z","timestamp":1784786776997,"version":"3.55.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"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","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) worldwide, and renal fibrosis is a key pathological feature driving disease progression. Polyphyllin II (PPII), a steroidal saponin isolated from Rhizoma Paridis, has shown renoprotective potential; however, its effects and underlying mechanisms in DKD remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Network pharmacology was used to predict the potential targets and pathways of PPII in DKD. Experimental validation was performed in streptozotocin (STZ)-induced DKD mice treated with PPII (8\u00a0mg\/kg\/day for 4 weeks) and in high-glucose (HG)-stimulated glomerular mesangial cells (MCs). Renal function, urinary protein excretion, and histopathological changes were evaluated. Apoptosis was assessed by flow cytometry. Autophagy- and fibrosis-related proteins were examined by Western blotting, and autophagic flux was further evaluated using chloroquine (CQ). Rescue experiments were performed using 3-methyladenine (3-MA). Activation of the phosphoinositide 3-kinase\/protein kinase B\/mammalian target of rapamycin (PI3K\/AKT\/mTOR) pathway was assessed by measuring the phosphorylation levels of pathway components.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Network pharmacology identified PI3K\/AKT signaling as a potentially important pathway involved in the effects of PPII in DKD. In DKD mice, PPII partially improved renal dysfunction, as reflected by reduced urinary protein excretion, serum creatinine (Scr), and uric acid (UA) levels, as well as increased serum albumin (Alb). Histological analyses showed that PPII attenuated glomerular hypertrophy, mesangial expansion, and renal fibrosis. In HG-stimulated MCs, PPII reduced apoptosis and decreased the expression of fibrosis-related proteins. In both renal tissues and MCs, PPII treatment was associated with reduced p62 expression and an increased LC3-II\/LC3-I ratio. CQ-based autophagic flux analysis suggested that PPII may enhance autophagic flux, while 3-MA partially attenuated the anti-fibrotic effects of PPII. In addition, PPII partially reduced HG- and DKD-associated activation of the PI3K\/AKT\/mTOR pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PPII alleviated renal injury and fibrosis in experimental DKD models and was associated with improved autophagy and reduced fibrotic responses. These effects may be related to modulation of the PI3K\/AKT\/mTOR signaling pathway. PPII may therefore represent a potential therapeutic candidate for DKD, although further studies are needed to clarify its molecular mechanisms and translational relevance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1822990","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:39:30Z","timestamp":1784785170000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyphyllin II attenuates renal fibrosis in diabetic kidney disease partly through regulation of autophagy and PI3K\/AKT\/mTOR signaling"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaozhu","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Nephrology, The Fifth Affiliated Hospital of Southern Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University","place":["Harbin, Heilongjiang, China"]},{"name":"Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinfang","family":"Qin","sequence":"additional","affiliation":[{"name":"Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixin","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Fifth Affiliated Hospital of Southern Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s12933-025-02643-6","article-title":"The impact of metformin on kidney disease progression and mortality in diabetic patients using SGLT2 inhibitors: a real-world cohort study","volume":"24","author":"Agur","year":"2025","journal-title":"Cardiovasc Diabetol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/nrneph.2017.142","article-title":"Modelling diabetic nephropathy in mice","volume":"14","author":"Azushima","year":"2018","journal-title":"Nat. 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