Hypericum perforatum L. Nanoemulsion Mitigates Cisplatin-Induced Chemobrain via Reducing Neurobehavioral Alterations, Oxidative Stress, Neuroinflammation, and Apoptosis in Adult Rats

Abstract

Cisplatin (Cis) is a potent chemotherapeutic agent; however, it is linked with oxidative stress, inflammation, and apoptosis, which may harmfully affect the brain. Hypericum perforatum L. (HP L.) is a strong medicinal plant, but its hydrophobic polyphenolic compounds limit its activity. Therefore, our study aimed to investigate the neuroprotective action of HP L. and its nanoemulsion (NE) against Cis-induced neurotoxicity. The prepared HP.NE was subjected to characterization. The droplet size distribution, surface charge, and morphology were evaluated. In addition, an in vitro dissolution study was conducted. Compared to Cis-intoxicated rats, HP L. and HP.NE-treated rats displayed improved motor activity and spatial working memory. They also showed an increase in their antioxidant defense system and a reduction in the levels of pro-inflammatory cytokines in the brain. Moreover, they showed an increase in the expression levels of the PON-3 and GPX genes, which are associated with a reduction in the brain levels of COX-2 and TP-53. These findings were confirmed by reducing the immunohistochemical expression of nuclear factor kappa (NF-ƘB) and enhanced Ki-67 levels. In conclusion, HP L. is a promising herb and could be used as an adjuvant candidate to ameliorate chemotherapeutic-induced neurotoxicity. Moreover, HP.NE has superior activity in lessening Cis-induced oxidative stress, inflammation, and apoptosis in brain tissue.

Effect of tangeretin on cisplatin‐induced oxido‐inflammatory brain damage in rats

“…As is known, 8‐OHdG is one of the most important biomarkers of oxidative stress and is an important indicator used in the determination of DNA damage 49 . Khalil et al., 50 reported that 8‐OHdG levels were increased and the degree of DNA damage was increased in the CIS group. Similarly, Mansour et al., reported that 8‐OHdG levels increased in the brain tissues of CIS‐treated rats and this was associated with the increase in ROS production caused by CIS and acceleration of oxidative DNA damage 51 .…”

Oxidative Damage as a Fundament of Systemic Toxicities Induced by Cisplatin—The Crucial Limitation or Potential Therapeutic Target?

“…The results suggested that the tested compound was able to diminish cisplatin-induced cortical toxicity via multiple signaling pathways, lowering the behavioral changes, inflammation response, and levels of oxidative stress. Another study conducted on Wistar albino rats tested the effects of nanoemulsion formed with Hypericum perforatum L. extract on cisplatin-induced cognitive impairment, a state often caused by most chemotherapeutics [82]. After the administration of Hypericum nanoemulsion for 21 days, the toxicity in animals was induced by a single dose of cisplatin (10 mg/kg, i.p.).…”

O Papel Da Crononutrição Na Resistência Insulínica E Glicemia Pós-Prandial: Mini Revisão

“…Para a seleção de artigos foram utilizados os quatro elementos da estratégia PICO, uma metodologia para nortear a pesquisa (SANTOS et al 2007) (TABELA 1). Foram incluídos artigos em inglês, publicados no período de 5 anos (2018)(2019)(2020)(2021)(2022)(2023). Os artigos selecionados foram do tipo intervencional (experimentais), que utilizaram ratos apenas da linhagem Wistar, para melhor comparação entre apenas uma mesma linhagem de rato.…”