急性肾损伤和慢性肾纤维化是难以解决的病理过程，而有限的策略能够有效应对这些问题。白豆蔻酮（CAD）是一种具有出色抗氧化、抗炎作用和令人满意生物安全性的类黄酮。在我们的研究中，我们成功建立了肾缺血/再灌注（I/R）和单侧输尿管阻塞（UUO）的动物和细胞模型，以确认CAD是否具有保护作用和潜在机制。动物实验表明，CAD应用（100mg/kg）显著改善组织损伤，并改善肾功能。同时，在UUO手术后连续口服CAD有效抑制了肾纤维化，此现象可通过苏木精-伊红（H&E）、西鲁红和马松染色以及胶原I、α-平滑肌肌动蛋白（α-SMA）、胶原III和纤维连接蛋白的下调的mRNA和蛋白表达得到确认。有趣的是，在转化生长因子β1（TGF-β1）刺激和低氧/复氧（H/R）暴露的人肾细胞(HK-2)中，CAD的保护作用再次得到验证。同时，我们进行了生物信息学分析并构建了“成分-靶点-通路-疾病”网络，以得出CAD保护的潜在机制可能是通过调节氧化应激、炎症、细胞凋亡和有丝分裂活化蛋白激酶（MAPK）通路。此外，实验数据证实，CAD明显降低了活性氧（ROS）产生和丙二醛（MDA）含量，同时降低了炎症标志物（肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β））的mRNA和蛋白表达，抑制了凋亡，证明在肾I/R和UUO模型中减少了P53、BAX、活化的半胱天冬酶-3和凋亡率。此外，CAD对抑制氧化应激和炎症的影响归因于其能提升抗氧化酶活性，包括双氧水酶、超氧化物歧化酶1（SOD1）和超氧化物歧化酶2（SOD2），以及抑制与炎症相关的MARK/NF-κB（MAPK/NF-κB）信号通路。总之，白豆蔻酮恢复了抗氧化能力，阻断了氧化应激，并抑制了MAPK/NF-κB信号通路以减轻炎症反应，从而在体外和体内缓解了I/R引起的急性肾损伤和UUO引起的肾纤维化的情况，这表明了白豆蔻酮在缓解急性和慢性肾损伤方面的潜在治疗优势。

Acute kidney injury and chronic renal fibrosis are intractable pathological processes to resolve, yet limited strategies are able to effectively address them. Cardamonin (CAD) is a flavonoid with talented antioxidant, anti-inflammatory capacity, and satisfactory biosafety. In our study, animal and cellular models of renal ischemia/reperfusion (I/R) and unilateral ureteral obstruction (UUO) were successfully constructed to confirm whether CAD confers protective effects and underlying mechanisms. Animal experiments demonstrated that CAD application (100 mg/kg) distinctly ameliorated tissue damage and improved renal function. Meanwhile, the continuous oral administration of CAD after UUO surgery efficiently inhibited renal fibrosis as confirmed by hematoxylin-eosin (H&E), Sirius red, and Masson staining as well as the downregulated mRNA and protein expression of collagen I, α-smooth muscle actin (α-SMA), collagen III, and fibronectin. Interestingly, in transforming growth factor β1 (TGF-β1)-stimulated and hypoxia/reoxygenation (H/R)-exposed human kidney-2 (HK-2) cells, protective effects of CAD were again authenticated. Meanwhile, we performed bioinformatics analysis and constructed the "ingredient-target-pathway-disease" network to conclude that the potential mechanisms of CAD protection may be through the regulation of oxidative stress, inflammation, apoptosis, and mitogen-activated protein kinase (MAPK) pathway. Furthermore, experimental data validated that CAD evidently decreased the reactive oxygen species (ROS) production and malondialdehyde (MDA) content while depressing the mRNA and protein expression of inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and Il-1β) and inhibiting apoptosis as evidenced by decreased levels of P53, BAX, cleaved caspase-3, and apoptotic rate in renal I/R and UUO models. In addition, the impact of CAD on restraining oxidative stress and inflammation was attributed to its ability to elevate antioxidant enzyme activities including catalase, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) and to inhibit the inflammation-associated MARK/nuclear factor-κB (MAPK/NF-κB) signaling pathway. In conclusion, cardamonin restored the antioxidative capacity to block oxidative stress and suppressed the MAPK/NF-κB signaling pathway to alleviate inflammatory response, thus mitigating I/R-generated acute kidney injury/UUO-induced renal fibrosis in vivo and in vitro, which indicated the potential therapeutic advantage of cardamonin in attenuating acute and chronic kidney injuries.