Oridonin Attenuates Cisplatin-Induced Ovarian Injury by Modulating Oxidative Stress, Inflammation, and TGF-β1/Smad3-Mediated Fibrosis in Rats

Background and Objectives: The aim of this study is to evaluate the effects of oridonin on a cisplatin-induced ovarian injury rat model. Materials and Methods: Thirty female rats were divided into three groups. Group 1: control; group 2: cisplatin; group 3: cisplatin plus oridonin group. In groups 2 and 3, the rats were injected with 2.5 mg/kg (twice weekly) cisplatin intraperitoneally (i.p.) for 4 weeks. In Group 3, rats received oridonin (10 mg/kg/day, i.p.). At the end of the study, the ovaries were removed in all groups. Histopathologic analysis and follicle counting were performed. Plasma anti-Müllerian hormone (AMH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels were measured, while ovarian transforming growth factor-beta 1 (TGF-β1), SMAD family member 3 (SMAD3), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels were evaluated. Results: Oridonin alleviated cisplatin-induced histopathological changes in the ovarian tissue. The numbers of primordial, primary, secondary, and tertiary follicles were significantly decreased, while ovarian fibrosis was significantly increased in Group 2 compared with Group 1 (p < 0.05). Co-treatment with oridonin statistically significantly increased follicle counts at all developmental stages and markedly reduced ovarian fibrosis in group 2 compared with group 3. Compared with Group 1, AMH decreased, whereas MDA, TNF-α, TGF-β1, SMAD3, and TIMP-1 increased in Group 2 (p < 0.001); these alterations were markedly attenuated in Group 3. Conclusions: These findings suggest that oridonin may exert protective effects against cisplatin-induced ovarian injury.