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This research delves into the influence of H2Valdien derivatives on the proliferation, migration, and apoptosis induction in hepatoma carcinoma cells (HepG2, Huh-7, and SMMC-7721), with a specific emphasis on inhibiting epithelial–mesenchymal transition (EMT) through modulation of the Hedgehog (Hh) signaling pathway. Utilizing the cell counting kit-8 method, flow cytometry, TUNEL assay, wound healing, and transwell assays, we observed a dose-dependent growth arrest and apoptosis induction in HepG2, Huh-7, and SMMC-7721 cells. Notably, H2Valdien derivatives exhibited a capacity to reduce migration and invasion, impacting the expression of EMT-associated proteins such as N-cadherin, vimentin, and E-cadherin. Mechanistically, these derivatives demonstrated the inhibition of the Hh signaling pathway by inactivating Sonic Hh (Shh) and smoothened proteins. This study underscores the robust antiproliferative and apoptosis-inducing effects of H2Valdien derivatives on hepatoma carcinoma cells and elucidates their regulatory role in EMT through modulation of the Hh signaling pathway, providing valuable insights for potential therapeutic interventions.

This study explores the compelling antitumor properties of VALD‐2, a synthetic Schiff base ligand known for its low toxicity. The focus is on investigating VALD‐2's protective role against cisplatin‐induced acute kidney injury (AKI) in mice, with a specific emphasis on mitigating oxidative stress and inflammation. The study involves daily intraperitoneal injections of amifostine or VALD‐2 over 7 days to establish an AKI model. Subsequently, mice were assigned to normal control, cisplatin group, cisplatin + amifostine group, and cisplatin + VALD‐2 10 mg/kg group, cisplatin + VALD‐2 20 mg/kg, and cisplatin + VALD‐2 40 mg/kg. Kidney injury is assessed through serum blood urea nitrogen (BUN) and creatinine (Cr) activity assays. Levels of inflammatory factors, tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6), in kidney tissue of mice were assessed through enzyme‐linked immunosorbent assay (ELISA). The protective effect of VALD‐2 is further examined through HE staining to observe pathological changes in kidney injury. The ultrastructural changes of renal cells and tubular epithelial cells were observed by electron microscopy under experimental conditions, indicating the effect of VALD‐2 on reversing cisplatin‐induced renal injury. The study delves into VALD‐2's protective mechanisms against cisplatin‐induced kidney injury by using western blot analysis to assess the expression levels of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and malondialdehyde (MDA) in kidney tissues. VALD‐2 demonstrates significant improvement in cisplatin‐induced AKI, as evidenced by increased BUN and Cr levels. It effectively protects kidney tissue from oxidative damage, enhancing SOD and GSH‐Px activities while reducing MDA levels. The study also reveals a decrease in TNF‐α and IL‐6 levels, supported by ELISA results, and histological findings confirm anti‐nephrotoxic effects. Western blot analysis shows an upregulation of antioxidant enzymes (SOD, GSH‐Px) and a reduction in MDA production. VALD‐2 emerges as a promising mitigator of cisplatin‐induced AKI, showcasing its ability to enhance oxidative stress‐related protein expression. The findings suggest VALD‐2 as a potential therapeutic agent for protecting against cisplatin‐induced kidney injury. Highlights: VALD‐2 is a yellow precipitate, a Schiff base ligand synthesized by mixing diethylene‐triamine and o‐vanillin and insoluble in 0.9% sodium chloride. It has been also reported that which forms complexes with most metals and has potential antibacterial, antiviral, and anticancer effects.In our previous study, we found that VALD showed antitumor effects both in vivo and in vitro. In recent years, the antitumor activities of some Schiff base ligands have been widely reported.Our study revealed for the first time that VALD‐2 alleviates cisplatin‐induced acute renal injury by inhibiting renal inflammation and enhancing the endogenous antioxidant system, which provides a molecular basis for the new drug treatment of cisplatin‐induced acute renal injury. [ABSTRACT FROM AUTHOR]