Gossypetin (GTIN), known as 3,5,7,8,3′,4′-hexahydroxyflavone, has been demonstrated to exert anti-atherosclerotic potential against apoptotic injury in oxidized low-density lipoprotein-incubated endothelial cells, and atherosclerotic lesions of cholesterol-fed rabbits. However, the effect and underlying mechanism of GTIN on abnormal vascular smooth muscle cells (VSMCs) proliferation and migration, a major event in the pathogenesis of atherosclerosis, is still unknown. In this study, non-cytotoxic doses of GTIN abolished the VSMCs A7r5 proliferation and cell-cycle S phase distribution. The GTIN-arrested G0/G1 phase might be performed by increasing the expressions of phosphorylated p53 and its downstream molecules that inhibit the activation of cyclin E/cyclin-dependent kinase (cdk)-2, blocking retinoblastoma protein (Rb) phosphorylation and the subsequent dissociation of Rb/transcription factor E2F1 complex. In addition, the results indicated that GTIN inhibited VSMCs wound-healing and migratory abilities through reducing matrix metalloproteinase (MMP)-9 activity and expression, as well as down-regulating protein kinase B (PKB)/nuclear factor-kappaB (NF-κB) signaling. GTIN also revealed potential in diminishing reactive oxygen species (ROS) generation. These findings suggested the inhibitory effects of GTIN on VSMCs dysfunction could likely lead to the containment of atherosclerosis and other cardiovascular illness.

Cisplatin has been considered a chemotherapeutic drug for treating human tumors, and one of the noteworthy side effects of cisplatin is nephrotoxicity. Amelioration of cisplatin-induced nephrotoxicity is necessary. Lotus seedpod extract (LSE) mainly composed of quercetin-3-glucuronide has been revealed for antioxidant and anti-tumor effects. However, the effects of LSE on cisplatin-induced nephrotoxicity are still unknown. This study aims to explore the in vitro and in vivo protective effect and possible mechanism of LSE on cisplatin-induced nephrotoxicity. Results showed that co-treatment of LSE with cisplatin raised the viability of rat renal tubular epithelial NRK−52E cells and decreased oxidative stress and cell apoptosis when compared to the cells treated with cisplatin alone. The molecular mechanisms analyzed found that LSE could reduce the expressions of apoptotic factors, including Bax, Bad, t-Bid, and caspases. In the in vivo study, LSE improved the cisplatin-induced levels of serum markers of kidney function, glomerular atrophy, and the degree of apoptosis in the kidneys. This is the first study to display that LSE prevents cisplatin-induced nephrotoxicity by reducing oxidative stress and apoptosis. Thus, LSE could be a novel and natural chemoprotective agent for cisplatin chemotherapy in the future.

Pulmonary fibrosis involves oxidative stress, inflammation, and fibroblast-to-myofibroblast transition (FMT). Quercetin-3-glucuronide (Q3G) exhibits antioxidant and anti-inflammatory properties; however, its antifibrotic effects remain unclear. This study aimed to investigate the protective role of Q3G in epithelial injury-induced fibroblast activation, with a focus on nuclear factor erythroid 2-related factor 2 (Nrf2) and autophagy regulation. First, the decreased expressions of Nrf2 and an autophagy marker LC3 were detected in human emphysema compared with normal subjects. Further results demonstrated Q3G enhanced both coexpressions, while suppressing reactive oxygen species (ROS), interleukin (IL)-1β, IL-6, and extracellular matrix (ECM) deposition. The protective effects of Q3G were significantly reversed by Nrf2 silencing or autophagy inhibition. The Q3G-induced colocalization of Nrf2 and LC3 suggests a functional coupling between these pathways, which contributes to redox homeostasis and the attenuation of fibrosis. These findings indicate that Q3G mitigates oxidative stress, inflammation, and FMT via the coordinated activation of Nrf2 and autophagy, highlighting its therapeutic potential in pulmonary fibrosis.