Curcumin is among the most well-studied natural substances, known for its biological actions within the central nervous system, its antioxidant and anti-inflammatory properties, and human health benefits. However, challenges persist in effectively utilising curcumin, addressing its metabolism and passage through the blood–brain barrier (BBB) in therapies targeting cerebrovascular diseases. Current challenges in curcumin’s applications revolve around its effects within neoplastic tissues alongside the development of intelligent formulations to enhance its bioavailability. Formulations have been discovered including curcumin’s complexes with brain-derived phospholipids and proteins, or its liposomal encapsulation. These novel strategies aim to improve curcumin’s bioavailability and stability, and its capability to cross the BBB, thereby potentially enhancing its efficacy in treating cerebrovascular diseases. In summary, this review provides a comprehensive overview of molecular pathways involved in interactions of curcumin and its metabolites, and brain vascular homeostasis. This review explores cellular and molecular current aspects, of curcumin-based effects with an emphasis on curcumin’s metabolism and its impact on pathological conditions, such as neurodegenerative diseases, schizophrenia, and cerebral angiopathy. It also highlights the limitations posed by curcumin’s poor bioavailability and discusses ongoing efforts to surpass these impediments to harness the full therapeutic potential of curcumin in neurological disorders.

Liver fibrosis can develop after sustained oxidative stress and inflammatory signaling and transforming growth factor-β (TGF-β) is a key profibrotic mediator. Rutin (Ru) is a plant-derived flavonoid with antioxidant and anti-inflammatory effects, but with limited bioavailability, which impedes therapeutic efficacy. This study investigated the hepatoprotective potential of rutin-phytoreduced gold nanoparticles (RuAuNPs) in a thioacetamide (TAA)-induced rat model of liver fibrosis. RuAuNPs were spherical, 18nm diameter (transmission electron microscopy -TEM) and exhibited SPR peak at 523nm (UV–Vis spectroscopy). Following liver fibrosis induction, animals were treated with free rutin or RuAuNPs. Oxidative stress (spectrophotometry, fluorimetry), inflammation (ELISA) and liver morphology (histopathology, TEM) were evaluated. TAA induced hepatic injury and fibrotic remodeling, associated with elevated TGF-β expression, oxidative stress, and inflammation. Free rutin showed limited recovery of liver parameters. RuAuNP treatment significantly improved hepatic histology and ultrastructure, reduced TGF-β and pro-inflammatory cytokine levels (TNFα, IL1β, IL6), decreased oxidative stress damage (lipid peroxidation), restored glutathione redox balance, and enhanced superoxide dismutase activity. Improvement in the AST/ALT ratio suggested early functional recovery, despite persistent aminotransferase elevation. Overall, RuAuNPs enhanced rutin’s antifibrotic and hepatoprotective effects by targeting oxidative and inflammatory pathways and can represent an effective delivery system for rutin in liver fibrosis therapy.

Liver fibrosis is driven by persistent oxidative stress and inflammatory signaling, with transforming growth factor-β (TGF-β) acting as a key profibrotic mediator. Rutin (Ru) is a plant-derived flavonoid with antioxidant and anti-inflammatory effects, but its low bioavailability limits therapeutic efficacy. This study investigated whether rutin-phytoreduced gold nanoparticles (RuAuNPs) enhanced rutin delivery leading to antifibrotic and anti-inflammatory effects in a rat model of liver fibrosis. Liver fibrosis was induced by oral administration of thioacetamide (TAA, 150 mg/kg body weight, p.o.) for six weeks. Following fibrosis induction, the animals were treated with free rutin (30 mg/kg body weight), RuAuNPs (0.3 mg/kg body weight), or AuNPs (0.3 mg/kg body weight), both expressed as nanoparticle mass, all administered orally for four weeks. RuAuNPs were synthesized by green rutin-mediated reduction and further characterized by TEM, DLS, and FTIR spectroscopy; they were spherical, showing an average hydrodynamic size of 104.1 nm (PDI 0.345). FTIR confirmed rutin capping. Biological effects were evaluated by liver morphology (H&E histology, TEM), biochemical assessment of liver aminotransferases and glico-lipidic status, ELISA and spectrophotometry measurement of redox biomarkers (lipid peroxidation, glutathione status, antioxidant enzymes), cytokines (TNF-α, IL-1β, IL-6), and TGF-β. TAA-induced hepatic injury and remodeling with increased profibrotic signaling, oxidative stress, and inflammation. Free rutin slightly ameliorated the liver damage, whereas RuAuNP improved histological features, reduced TGF-β and pro-inflammatory cytokines, decreased lipid peroxidation, and supported antioxidant defenses. Overall, RuAuNP may enhance rutin efficacy in TAA-induced liver fibrosis, with novelty stemming from the integrated in vivo evaluation of tissue changes and key profibrotic/oxidative/inflammatory pathway.

Parkinson’s disease (PD) remains incompletely understood despite its high social and economic burden, with oxidative stress, neuroinflammation, and mitochondrial dysfunction recognized as central pathogenic mechanisms. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a complex I inhibitor, is widely used as a model of dopaminergic neurodegeneration, while growing evidence highlights the gut–liver–brain and kidney–brain axes as important contributors to PD progression. Within this framework, trimethylamine N-oxide (TMAO) has emerged as a molecule of interest, linked to dementia risk and proinflammatory effects. Our study aimed to evaluate the peripheral oxidative and inflammatory consequences of acute and semi-acute MPTP exposure, alone and in combination with TMAO. In total, 96 male CD-1 mice were equally divided across two experimental settings: a semi-acute protocol (30 mg/kg i.p., MPTP once daily for five consecutive days) and an acute protocol (20 mg/kg i.p., four administrations of MPTP at two-hour intervals), with TMAO administration remaining identical across both experimental settings. The animals were randomized into four groups (control group, a TMAO-only group (40 mg/kg/day, gavage, days 0–42), an MPTP-only group, and a combined TMAO + MPTP group), with MPTP showing consistently depleted liver SOD activity across both models. In the liver, MPTP showed consistently depleted SOD activity in both models, whereas glutathione disruption and lipid peroxidation were most evident in the combined TMAO + MPTP group. These effects were explained mainly by the additive main effects of MPTP and TMAO, as no significant MPTP × TMAO interaction was found for any oxidative stress marker. Nonetheless, a significant MPTP × TMAO interaction was confirmed for liver and kidney IL-1β in the acute model. IL-1β and IL-6 were significantly elevated in the liver and kidney by both MPTP alone and its combination with TMAO, with the combined groups consistently showing the largest increases (TMAO + MPTP semi-acute vs. control and vs. TMAO, p < 0.001–0.01; TMAO + MPTP acute vs. all groups, p < 0.0001–0.01). In the kidney, the contribution of MPTP and TMAO to oxidative stress was model-dependent: in the semi-acute protocol, both MPTP and TMAO contributed to increased MDA and glutathione ratio disruption, while in the acute protocol, TMAO alone was the dominant driver of SOD depletion and MDA elevation, with their combination further amplifying IL-6 secretion. TMAO also independently drove lipid peroxidation in the heart and intestine. The acute MPTP model produced more extensive redox imbalance independently of TMAO, whereas in the semi-acute model, a comparable degree of redox disruption was only achieved through combined TMAO + MPTP exposure.