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Our study found that Panax notoginseng saponins (PNS) improve lipid metabolism and prevent AS in steroid\u2010resistant LN by up\u2010regulating PPAR\u03b3, though mechanisms are unclear. Recent research highlights the roles of macrophages, with M1 M\u00f8 promoting inflammation and M2 M\u00f8 providing protection, as PPAR\u03b3 influences M\u00f8's polarization, linking it to inflammation and M2 polarization, necessitating further investigation. Therefore, we conduct this study to investigate the regulatory effect of PNS on the \u201cM\u00f8 M2 polarization\u2010PPAR\u03b3\u201d positive regulation, endeavoring to elucidate its therapeutic potential of delaying AS and reversing SR in LN. PPAR\u03b3 expression in polarized M\u00f8 was measured via PCR and WB, while M1\/M2 biomarkers and cytokines, influenced by PPAR\u03b3 modulation, were assessed using flow cytometry and ELISA. In mouse M\u00f8 treated with PNS, IL\u20104, or both, PPAR\u03b3 and cytokines were measured. ICR and MRL\/lpr mice were used to establish an in\u00a0vivo SR model to confirm PNS's role in M2 polarization of M\u00f8 and AS protection by analyzing blood lipid levels, iNOS, Lp(a), and apoptosis rates through WB, immunohistochemistry, HE\u2010staining, and TUNEL. PNS's efficacy in renal protection and SR reversal was evaluated through Scr, BUN, urine protein, renal pathology, and P\u2010gp; MDR1 expression was assessed via biochemical detection, HE\u2010staining, flow cytometry, and WB. This study confirmed that PNS upregulates PPAR\u03b3 and promotes M2 polarization, improving abdominal aorta pathology and delaying AS. It also enhances renal function and reverses SR by reducing P\u2010gp and MDR1. This study shows that PNS promotes M\u00f8 polarization to M2 and enhances PPAR\u03b3 expression, effectively preventing AS, improving renal function, and reversing SR in LN, offering insights for LN treatment and expanding PNS's therapeutic benefits for future research.<\/jats:p>","DOI":"10.1002\/ptr.70192","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T11:13:59Z","timestamp":1768994039000},"page":"1274-1289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>Panax notoginseng<\/i>\n                    <\/scp>\n                    Saponins Prevents Atherosclerosis and Reverse Steroid\u2010Resistance in Lupus Nephritis via Promoting the \u201c\n                    <scp>M2<\/scp>\n                    \u2010Polarization of Macrophages\u2014\n                    <scp>PPAR\u03b3<\/scp>\n                    \u201d Positive 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