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.

Breast cancer is a prevalent tumor and causes deadly metastatic complications. Myriad cancer types, including breast cancer, are effectively treated by methotrexate (MTX). However, MTX hydrophobicity, adverse effects and the development of resistance have inspired a search for new effective strategies to overcome these challenges. These may include the addition of a bioenhancer and/or encapsulation into appropriate nano-based carriers. In the present study, the anticancer effect of MTX was fortified through dual approaches. First, the concomitant use of piperine (PIP) as a bioenhancer with MTX, which was investigated in the MCF-7 cell line. The results depicted significantly lower IC₅₀ values for the combination (PIP/MTX) than for MTX. Second, PIP and MTX were individually nanoformulated into F-127 pluronic nanomicelles (PIP-NMs) and F-127/P-105 mixed pluronic nanomicelles (MTX-MNMs), respectively, validated by several characterization techniques, and the re-investigated cytotoxicity of PIP-NMs and MTX-MNMs was fortified. Besides, the PIP-NMs/MTX-MNMs demonstrated further cytotoxicity enhancement. The PIP-NMs/MTX-MNMs combination was analyzed by flow cytometry to understand the cell death mechanism. Moreover, the in vivo assessment of PIP-NMs/MTX-MNMs was adopted through the Ehrlich ascites model, which revealed a significant reduction of the tumor weight. However, some results of the tumor markers showed that the addition of PIP-NMs to MTX-MNMs did not significantly enhance the antitumor effect.

Objectives: This research was designed to assess the impact and underlying pathways of the root aqueous extract of Moghat root (MRE) on metabolic syndrome (MS). Methods: The extract’s constituents were identified through HPLC analysis, followed by evaluation of its impact on lipid and glucose metabolism using in vitro and in vivo assays. Key findings: In a high-fat high-carbohydrate diet, streptozotocin animal model-induced MS, MRE increased fat accumulation and diminished the genes expression included in lipogenesis. Moreover, the extract enhanced obesity, the resistance of insulin, the amounts of lipid, oxidative stress, and hepatic function in MS rats after a 4 weeks intervention orally with the extract at 100 and 200 mg/kg related to metformin at 200 mg/kg after verification of diabetes. MRE decreased the expression of hepatic INSR, Srebf1, mTOR, PI3K, AKT, NF-κβ, and IL-6 through the PI3K/AKT/mTOR signaling pathway to inhibit inflammation and lipid accumulation and achieve its hypolipidemic effect. Moreover, MRE decreased the expression of MYD88 and p38 MAPK which was confirmed in liver tissue by using IHC analysis. Conclusions: Our data proposed that MRE could improve MS by improving lipid metabolism via numerous pathways and can be progressed into dietary supplements for the correction of MS.