Background/Objectives: Grape seed oil (GSO) is a potent source of dietary phytochemicals, particularly polyphenols and flavonoids, known for their health-promoting properties. This study aims to investigate the anticancer and hepatoprotective effects of a nanoemulsion formulation of grape seed oil (GSONE), to enhance the efficacy and bioavailability of its phytochemical constituents against solid tumors. Methods: Ninety female Swiss albino mice were divided into six groups: control, alone, GSONE alone, Ehrlich solid tumor (EST), EST treated with GSO, and EST treated with GSONE. Tumor development, growth performance, serum biochemistry, antioxidant status, hepatic histopathology, apoptotic gene expression, and flow cytometry analyses were assessed following 30 days of daily oral treatment. Results: GSONE significantly reduced tumor weight and volume (52.9%) and more effectively counteracted tumor-induced body weight loss than crude GSO. Treatment with GSONE normalized serum protein levels and improved liver function markers (AST, ALT, ALP, total bilirubin) to near-control values. Tumor markers (AFP, CEA) and oxidative stress indices (MDA, 8-OHdG) were markedly decreased, while activities of hepatic antioxidants (SOD, CAT, GPx, GSH) were restored. GSONE enhanced gene expression of pro-apoptotic markers (Bax, TP53, caspase-3, caspase-9), suppressed anti-apoptotic Bcl-2, and significantly increased the proportion of p53- and cleaved caspase-3-positive tumor cells. Liver histopathology and ultrastructure demonstrated normalized morphology and reduced damage in GSONE-treated mice. Multivariate analyses confirmed GSONE’s restorative effect compared to raw GSO. Conclusions: The delivery of dietary phytochemicals via nanoemulsion significantly enhances antitumor and hepatoprotective actions in a preclinical solid tumor model. These findings support the potential of phytochemical-rich edible oils, enhanced by nanotechnology, for dietary prevention and adjunctive management of cancer.

Amphotericin B (Amp-B/FZ), a first-line antifungal, is limited by dose-dependent nephrotoxicity. This study investigated the protective effects of hyperoside (HP), a dietary flavonoid, against FZ-induced renal toxicity in human proximal tubular (HK-2) cells. Molecular docking revealed strong binding affinities of HP with mitophagy (PINK1/PARKIN) and antioxidant (Nrf2/HO-1) regulators, contrasting with FZ’s preferential binding to mitochondrial complex I. FZ (30–60 µM) induced cytotoxicity (MTT/LDH), genotoxicity (comet assay), and bioenergetic disruption: ATP depletion (58%), mitochondrial complex I/III inhibition (42–67%), and PINK1/PARKIN dysregulation. FZ elevated reactive species (3.2-fold) and lipid peroxidation (2.8-fold) while suppressing catalase (64%) and superoxide dismutase (51%) activities. qPCR confirmed FZ-induced downregulation of NDUFS1, CYC1, CAT, and SOD2, alongside impaired Nrf2/HO-1 antioxidant signaling. Co-treatment with HP (20–40 µM) attenuated FZ toxicity, restoring ATP (1.8-fold), mitochondrial complex activities (35–49%), and antioxidant defenses (CAT:2.1-fold, SOD:1.7-fold). HP also normalized Nrf2/HO-1 expression and mitigated oxidative/genotoxic damage. These findings highlight HP’s dual role in countering FZ-induced mitochondrial dysfunction and oxidative stress, positioning it as a promising nephroprotective adjuvant. Further in vivo validation could advance HP’s clinical application in reducing antifungal-associated renal injury.

Background/Objectives: Arsenic (ARS) exposure is a major cause of kidney injury, driven by oxidative stress, inflammation, fibrosis, and apoptosis. This study evaluated the renoprotective effects of morin (MOR) and morin-loaded PLGA nanoparticles (MOR–PGNPs) against ARS-induced nephrotoxicity in rats. Methods: Sixty male Sprague Dawley rats were randomly allocated into six groups (n = 10 per group). The control group received corn oil. The MOR group received MOR (100 mg/kg), and the MOR–PGNPs group received the same dose of MOR encapsulated in PLGA nanoparticles. ARS was administered at 10 mg/kg for 14 days. Co-treated groups received ARS together with either MOR or MOR–PGNPs, with a 28 min interval between administrations. Renal function markers (serum urea, creatinine, uric acid, renal KIM-1), oxidative stress and antioxidant parameters (Nrf2/HO-1, CAT, SOD, GPx, ROS, MDA), inflammatory mediators (TLR4/NF-κB, TNF-α, IL-6, IL-1β), fibrotic markers (TGF-β1, fibronectin), and apoptotic proteins (caspase-3, caspase-8, Bax, Bcl-2) were assessed, alongside histopathological and ultrastructural evaluations. Results: ARS exposure significantly impaired renal function, increased KIM-1, suppressed Nrf2/HO-1 signaling, reduced antioxidant enzyme activities, and elevated ROS and MDA levels. It also activated TLR4/NF-κB signaling, upregulated pro-inflammatory cytokines and fibrotic markers, and increased pro-apoptotic proteins while downregulating Bcl-2. MOR co-treatment partially ameliorated these alterations. MOR–PGNPs produced potentially enhanced protection, restoring kidney function markers, enhancing antioxidant defenses, and markedly attenuating inflammation, fibrosis, and apoptosis. Histopathological and ultrastructural analyses confirmed preservation of glomerular and tubular architecture, mitochondrial integrity, and minimal cytoplasmic vacuolization in the MOR–PGNPs group. Conclusions: MOR–PGNPs at 100 mg/kg effectively mitigated ARS-induced renal damage through antioxidant, anti-inflammatory, antifibrotic, and anti-apoptotic mechanisms, supporting PLGA-based morin nanoparticles as a promising and safe renoprotective strategy.

Colorectal cancer (CRC) is driven by oxidative stress, chronic inflammation, and disruption of cytoprotective signaling pathways. This study aimed to evaluate whether poly(lactic-co-glycolic acid) (PLGA)-based nanoparticle delivery enhances the chemoprotective efficacy of paeonol against 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis, with a focus on modulation of the NRF2/HO-1 pathway. Sixty male Wistar rats were randomly assigned to six groups: control, paeonol (PNL), PNL-PLGA, DMH, DMH + PNL, and DMH + PNL-PLGA. CRC was induced using DMH over 10 weeks. Serum tumor biomarkers (AFP, CEA, CA19-9, CA125, CA15-3), oxidative stress markers (ROS, MDA, antioxidant enzymes), inflammatory cytokines, DNA damage, apoptosis- and autophagy-related gene expression, and hepatic and renal function were assessed. Histopathological and ultrastructural analyses of colonic tissues were performed. DMH exposure was markedly associated with increased tumor biomarkers, oxidative stress, and inflammatory mediators, DNA damage, and impaired liver and kidney function. It was also associated with the restoration of NRF2/HO-1 signaling, improved redox balance, suppression of inflammation, reduction in DNA damage, and preservation of regulated NRF2/HO-1 signaling, antioxidant defenses, autophagy markers, and apoptotic proteins, as well as severe histological and ultrastructural alterations. Free paeonol partially attenuated these changes. In contrast, PNL-PLGA was significantly associated with restoring NRF2/HO-1 signaling, improving redox balance, suppressing inflammation, reducing DNA damage, and preserving colonic architecture and ultrastructure. These findings demonstrate that a PLGA-based nanoformulation of paeonol markedly improves its chemopreventive efficacy against DMH-induced CRC, primarily by activating NRF2/HO-1 signaling and modulating oxidative stress, inflammation, apoptosis, and autophagy, highlighting its potential as a promising nanotherapeutic strategy for colorectal cancer.