Jingrui Ji1,2,4†, Xiangdong Wang1,2,4†, Shuai Lian1,2,4, Haoyang Nie1,2,4, Fa Shi1,2,4, Fei Peng1,2,4, Mingxuan Zhao1,2,4, Ziauddin3, Hongliang Zhang1,2,4*, Peng Shang1,2,4*
1College of Animal Science, Xizang Agriculture and Animal Husbandry University, Linzhi 860000, Xizang, China
2Key Laboratory of Tibetan Pig Genetic Improvement and Reproduction Engineering, Linzhi 860000, Xizang, China
3Center for Advanced Studies in Vaccinology & Biotechnology (CASVAB), University of Balochistan, Quetta, Pakistan
4Center for Provincial Departmental Collaborative Innovation of Xizang Characteristic Agriculture and Animal Husbandry Resources Research and Development, Linzhi 860000, Xizang, China
†These authors contributed equally to this work
*Corresponding author’s email: holingzhang@126.com; shangpeng1984@xza.edu.cn
Received: 17 June 2025 / Accepted: 23 September 2025 / Published Online: 10 October 2025
Abstract
Cisplatin is a widely used chemotherapeutic, yet its clinical use is limited by severe nephrotoxicity that often causes acute kidney injury (AKI). Effective, safe strategies to mitigate this remain unmet. We investigated the protective effect of Mirabilis himalaica extract (MHE) against cisplatin-induced acute kidney injury (AKI) in mice and explored its underlying mechanisms. Fifty mice were divided into five groups: control negative, cisplatin model (Control positive with 10 mg/kg), and three MHE treatment groups (10, 15, 20 mg/kg/day) following cisplatin (10 mg/kg). Controls and the model group received saline orally; treatment groups received MHE for 14 days. We measured serum creatinine (Cr), blood urea nitrogen (BUN), and β2-microglobulin (β2-MG) levels. Renal histopathology was assessed using H&E staining. Compared to the cisplatin model group, the medium-dose MHE group (15 mg/kg) significantly reduced serum Cr (41.8%, P < 0.01), BUN (24.5%, P < 0.01), and β2-MG levels (17.3%, P < 0.01). Histopathological analysis confirmed that medium-dose MHE markedly attenuated cisplatin-induced renal tubular damage, including epithelial cell swelling, necrosis, and inflammatory infiltration. While high-dose MHE (20 mg/kg) showed a trend in reducing β2-MG, this effect was not statistically significant. Low-dose MHE (10 mg/kg) did not demonstrate significant protection. MHE dose-dependently ameliorates cisplatin-induced AKI in mice, with optimal efficacy observed at 15 mg/kg. The renoprotective effects are associated with attenuation of renal dysfunction and histological damage, potentially mediated through suppression of oxidative stress and inflammation. These findings support MHE as a promising candidate for further development as a natural therapeutic agent against AKI.
Keywords: Acute Renal injury, Cisplatin, Inflammatory response, Mirabilis himalaica, Oxidative stress
