Oleoylethanolamide as a New Therapeutic Strategy to Alleviate Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (DOX) is one of the most common chemotherapeutic anti-cancer drugs. However, its clinical use is restricted by serious cardiotoxicity. Oleoylethanolamide (OEA), a structural congener of endocannabinoid anandamide, is the endogenous agonist of peroxisome proliferator activated-receptor α (PPARα) and transient receptor potential cation channel vanilloid-1 (TRPV1), and involved in many physiological processes. The present study aimed to determine whether OEA treatment protects against DOX-induced cytotoxicity (DIC) and gain insights into the underlying mechanism that mediate these effects. Our data revealed that Oleoylethanolamide treatment improved the myocardial structure in DOX-challenged mice by attenuating cardiac oxidative stress and cell apoptosis. OEA also alleviated DOX-induced oxidative stress and apoptosis dysregulation in HL-1 cardiomyocyte. These effects were mediated by activation of TRPV1 and upregulation of PI3K/ Akt signaling pathway. Inhibition of TRPV1 and PI3K reversed the protective effects of OEA. Taken together, our data suggested that OEA protects against DIC through a TRPV1- mediated PI3K/ Akt pathway.

A novel synthetic compound shows antioxidant and anti-inflammatory activity and alleviates cognitive deficits in rats for the treatment of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive dementia, and ß-amyloid (Aß) accumulation is widely regarded as the primary pathogenesis of AD. A new synthetic compound, 8-hydroxyquinoline-resveratrol derivative (E)-5-(4-hydroxystyryl)quinolin-8-ol (10c) was evaluated as a possible anti-AD agent. METHOD: (I) The total amount of ROS in SH-SY5Y cells was detected by dichlorofluorescein diacetate (DCFH-DA), and the antioxidant activity and neuroprotective effect of 10c in SH-SY5Y cells were evaluated; (II) Griess reagent was used to test the activity of Compound 10c against NO production in LPS-induced BV-2 microglial cells; (III) An automatic digital stereotaxic instrument was used to inject Aß25-35 into the brain to establish an AD animal model to evaluate the protective effect of compound 10c on Aß25-35-induced learning and memory dysfunction in rats. RESULTS: 10c exhibited far more potent antioxidant activity for both exogenous and endogenous reactive oxygen species (ROS) than trolox, resveratrol, and CQ (ROS production: 10c with 26.23% at 1.5 µM; resveratrol with 82.17% at 2.5 µM; CQ with 78.52% at 10 µM). 10c also shows good neuroprotective effects as an endogenous antioxidant in neuroblastoma cells. Moreover, Compound 10c also demonstrated effective inhibition of nitric oxide (NO) production (IC50 =3.10 µM) and IL-1ß production in BV-2 microglial cells which were treated with lipopolysaccharide (LPS). In the water maze test, the numbers of rats who crossed the former platform were increased significantly in both the 10c group (5.7±1.6) and positive control group (CQ, 5.1±1.7). Meanwhile, both 10c (43.8±5.5 s) and CQ (44.1±6.6 s) treatment could significantly prolong the time rats spent in the target quadrant compared to the vehicle-treated model group. These results demonstrated that 10c could alleviate the learning and memory dysfunction of rats induced by Aß25-35 to a certain extent. CONCLUSIONS: Altogether, compound 10c is a promising compound for the treatment of AD.

Peiminine inhibits the progression of colorectal cancer through up-regulating miR-760 via declining the expression of long noncoding RNA LINC00659.

Colorectal cancer (CRC) is a commonly diagnosed type of cancer globally. The molecular mechanism by which peiminine suppressed the progression of CRC is not fully addressed. The viability was assessed through cell counting kit 8 assay. Colony formation assay was used to analyze the colony formation ability. The metastasis was evaluated by transwell migration and invasion assays. Quantitative real-time PCR was performed to measure the expression of LINC00659 and miR-760 in CRC cells. The binding sites between miR-760 and LINC00659 were predicted by Starbase software and verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA-pull down assay. The in-vivo function of peiminine in CRC progression was confirmed by murine xenograft model. Peiminine inhibited the viability, colony formation and metastasis of CRC cells. Peiminine notably down-regulated the expression of LINC00659, while the expression of miR-760 was up-regulated by peiminine treatment. MiR-760 was a direct target of LINC00659 in CRC cells. The depletion of miR-760 attenuated the inhibitory effects of LINC00659 intervention on the viability, colony formation and metastasis of CRC cells. Peiminine restrained the progression of CRC through LINC00659 and miR-760. LINC00659 inhibited the growth of CRC tumors through LINC00659/miR-760 axis in vivo. Peiminine suppressed the development of CRC through inhibiting the viability, colony formation and metastasis of CRC cells via LINC00659/miR-760 axis. LINC00659/miR-760 axis might be an underlying target for CRC therapy.