Kara, Hulya; Tekiner, Deniz; Üstündağ, Hilal; Bayram, Cemil; Şebin, Saime Özbek; Özkanlar, Seçkin; Kara, Adem

Parkinson’s disease (PD) is characterized by progressive dopaminergic neuronal loss, with oxidative stress and neuroinflammation as critical pathological mechanisms. The blood–brain barrier presents a significant challenge for therapeutic delivery, while current treatments provide only symptomatic relief without halting disease progression. This study investigated the neuroprotective effects of astaxanthin-loaded citrate-coated silver nanoparticles (AST-AgNPs), leveraging their potent antioxidant properties, anti-inflammatory capacity, and enhanced blood–brain barrier penetration. In vitro cytotoxicity analyses were performed using 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y neuroblastoma cells, while in vivo experiments utilized a unilateral 6-OHDA-induced rat model. Following 14 days of treatment, comprehensive evaluations included behavioral assessments, biochemical analyses (MDA, GSH, SOD, TNF-α, IL-1β, IFN-γ), histopathology, immunohistochemistry (BrdU, tyrosine hydroxylase), and molecular analyses. Western blot measured CHOP, IRE1, ATF6, p-AKT, total AKT, caspase-3, and cleaved caspase-3, while RT-PCR quantified caspase-3, Bcl-2, Bax, PI3K, mTOR, Akt, CREB, and NF-κB-p65 expression. AST-AgNP treatment significantly ameliorated motor dysfunction, reduced neuroinflammation (TNF-α, IL-1β), improved oxidative stress parameters (MDA, GSH, SOD), and preserved dopaminergic neurons (all p < 0.05). Western blot revealed significant downregulation of ER stress markers (CHOP, IRE1, ATF6) and cleaved caspase-3, while restoring p-AKT and total AKT levels (p < 0.05). RT-PCR demonstrated decreased pro-apoptotic gene expression (caspase-3, NF-κB-p65) and increased anti-apoptotic Bcl-2 expression (p < 0.05). These findings demonstrate that AST-AgNPs provide neuroprotection through simultaneous modulation of ER stress and PI3K/Akt/mTOR pathways, representing a novel dual-pathway therapeutic strategy for PD addressing multiple pathological mechanisms through enhanced nanoparticle-mediated delivery.

Yeni, Yesim; Cicek, Betul; Hacimuftuoglu, Ahmet; Ozkaraca, Mustafa; Mokhtare, Behzad

Panax ginseng (PG) is a medicinal plant used for many years to treat many diseases. The current study aimed to investigate the possible prophylactic and therapeutic effects of PG extract on doxorubicin (DOX)-induced testicular toxicity in rats. 32 adult male Sprague–Dawley rats (200–250 g) were used in the experiment. The experimental groups were designed as control (normal saline, intraperitoneal), DOX (18 mg/kg, intraperitoneal), PG (200 mg/kg, gavage), and PG + DOX (200 mg/kg, gavage). After treatment, serum levels of testosterone, interleukin-1β (IL-1β), glutathione (GSH), luteinizing hormone (LH), superoxide dismutase (SOD), lactate dehydrogenase (LDH), catalase (CAT), follicle stimulating hormone (FSH), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) were measured. Then, gene expression, histopathological, and immunohistochemical analyses were performed on testicular tissues. Compared to DOX, treatment with PG + DOX showed a significant improvement in serum levels of FSH, testosterone, LH, TNF-α, IL-1β, MDA, SOD, LDH, GSH, and CAT. It was also observed that PG + DOX decreased nuclear factor-κB and cyclooxygenase-2 expression levels, increased androgen receptor expression, restored testicular histopathological structure, and significantly improved spermatogenesis. The results of the present study showed that PG may have an ameliorative effect against DOX-induced male reproductive toxicity, as DOX causes male reproductive toxicity. It can be concluded that PG is one of the effects that protect against DOX-induced testicular toxicity in rats by reducing lipid peroxidation and activating the antioxidant system. In light of this information, PG may be a useful agent to prevent the testicular toxicity observed in men receiving DOX treatment.