No abstract

IntroductionActivation of endogenous stem cell mobilization can contribute to myocardial regeneration after ischemic injury. This study aimed to evaluate the possible role of Avemar or Echinacea extracts in inducing mobilization and homing of CD34+ stem cells in relation to the inflammatory and hematopoietic cytokines in rats suffering from acute myocardial infarction (AMI).MethodsAMI was developed by two consecutive subcutaneous injections of isoprenaline (85 mg/kg). AMI rats were either post-treated or pre- and post-treated daily with oral doses of Avemar (121 mg/kg) or Echinacea (130 mg/kg). In whole blood, the number of CD34+ cells was measured by flow cytometry and their homing to the myocardium was immunohistochemically assessed. Serum creatine kinase, vascular endothelial growth factor, interleukin-8 and granulocyte macrophage colony stimulating factor were determined on days 1, 7 and 14 after AMI. Sections of the myocardium were histopathologically assessed.ResultsRats pre- and post-treated with Avemar or Echinacea exhibited substantial increases in the number of circulating CD34+ cells, peaking on the first day after AMI to approximately 13-fold and 15-fold, respectively, with a decline in their level on day 7 followed by a significant increase on day 14 compared to their corresponding AMI levels. Only post-treatment with Echinacea caused a time-dependent increase in circulating CD34+ cells on days 7 and 14. Such increases in circulating CD34+ cells were accompanied by increased homing to myocardial tissue 14 days after AMI. Interestingly, pre- and post-treatment with Avemar or Echinacea substantially increased serum creatine kinase on day 1, normalized its activity on day 7 and, on continued treatment, only Echinacea markedly increased its activity on day 14 compared to the corresponding AMI values. Moreover, both treatments modified differently the elevated serum vascular endothelial growth factor and the lowered granulocyte macrophage colony stimulating factor levels of the AMI group but did not affect the level of interleukin-8. These results were supported histopathologically by reduced inflammatory reactions and enhanced neovascularization.ConclusionAvemar and Echinacea extracts can effectively induce mobilization and homing of CD34+ stem cells to the myocardial tissue and thus may help in stem cell-based regeneration of the infarcted myocardium.

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. Lutein (LU) possesses numerous pharmacological activities, including anti‐inflammatory, antioxidant, and antiapoptotic effects. This study aimed to investigate the cardioprotective potential of LU in isoprenaline (ISO)‐induced MI and to explore its molecular mechanisms of action. AMI was induced by two consecutive subcutaneous doses of ISO (65 mg/kg; s.c.). The LU group was pretreated with LU (20 mg/kg; p.o.) for 30 days followed by ISO injections on Days 29 and 30. ISO group showed elevated serum creatine kinas‐MB (CK‐MB) and considerable electrocardiographic changes along with reduced ejection fraction compared to the normal group. LU pretreatment could decrease serum CK‐MB activity, normalize QRS and QTc intervals and restore ejection fraction compared to the untreated group. The ISO group demonstrated infarcted‐like lesions, which were ameliorated in the LU‐pretreated group. Immunohistochemical investigation revealed upregulated cardiac troponin T (cTn T) and desmin expressions in the LU‐pretreated group. LU pretreatment also enhanced cardiac thioredoxin (Trx) and glutathione (GSH) contents as well as reduced lipid peroxidation, compared to the untreated group. Importantly, LU pretreatment could downregulate long noncoding MI associated transcript (lncRNA MIAT) and thioredoxin‐interacting protein (TXNIP) and augment micro RNA (miR)‐200a and nuclear factor erythroid 2‐related factor 2 (Nrf2) expressions compared to the ISO group. Moreover, a significant inverse correlation between MIAT and miR‐200a was observed. In conclusion, this study revealed that LU could ameliorate ISO‐induced MI in rats by modulating MIAT/miR‐200a/Nrf2 pathway.

Patients with hyperthyroidism are commonly diagnosed with mood disorders. Naringin, (4′,5,7-trihydrocyflavanone-7-O-rhamnoglucoside), a natural bioflavonoid, has many neurobehavioral activities including anxiolytic and antidepressant properties. The role of Wingless (Wnt) signaling in psychiatric disorders is considered substantial but debatable. Recently, regulation of Wnt signaling by naringin has been reported in different disorders. Therefore, the present study aimed to investigate the possible role of Wnt/GSK-3β/β-catenin signaling in hyperthyroidism-induced mood disturbances and explore the therapeutic effects of naringin. Hyperthyroidism was induced in rats by intraperitoneal injection of 0.3 mg/kg levothyroxine for 2 weeks. Naringin was orally administered to rats with hyperthyroidism at a dose of 50 or 100 mg/kg for 2 weeks. Hyperthyroidism induced mood alterations as revealed by behavioral tests and histopathological changes including marked necrosis and vacuolation of neurons in the hippocampus and cerebellum. Intriguingly, hyperthyroidism activated Wnt/p-GSK-3β/βcatenin/DICER1/miR-124 signaling pathway in the hippocampus along with an elevation in serotonin, dopamine, and noradrenaline contents and a reduction in brain-derived neurotrophic factor (BDNF) content. Additionally, hyperthyroidism induced upregulation of cyclin D-1 expression, malondialdehyde (MDA) elevation, and glutathione (GSH) reduction. Naringin treatment alleviated behavioral and histopathological alterations and reversed hyperthyroidism-induced biochemical changes. In conclusion, this study revealed, for the first time, that hyperthyroidism could affect mental status by stimulating Wnt/p-GSK-3β/βcatenin signaling in the hippocampus. The observed beneficial effects of naringin could be attributed to increasing hippocampal BDNF, controlling the expression of Wnt/p-GSK-3β/β-catenin signaling as well as its antioxidant properties.

Despite the extensive therapeutic uses of diclofenac, it may cause several adverse effects, including hepatorenal injury. The antioxidant and anti-inflammatory properties of resveratrol, a polyphenolic compound, make the agent effective in ameliorating a variety of drug-induced injuries. This study investigated the potential beneficial effects of resveratrol on diclofenac-induced hepatorenal toxicity and explored the role of miR-144 and its relationship to oxidative stress and inflammation triggered by diclofenac. Rats were divided into four groups: control; diclofenac group received diclofenac (10 mg/kg/day, intraperitoneal [ip]) for 7 days; prevention group received resveratrol concomitantly with diclofenac for 7 days; and the treatment group received diclofenac for 7 days followed by resveratrol (20 mg/kg/day, per oral) for another 7 days. Diclofenac administration induced a significant increase in serum hepatorenal biomarkers and histopathological aberrations. In addition, diclofenac upregulated miR-144 while reducing nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels and glutathione (GSH) content.Moreover, diclofenac induced tissue inflammation and apoptosis as evidenced by increased protein expression of nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), and caspase-3. Intriguingly, resveratrol prevention or treatment significantly mitigated the toxic effects of diclofenac as manifested by normalization of the hepatorenal functions and amelioration of the histopathological changes.Resveratrol also triggered miR-144 downregulation with Nrf2 upregulation.Consequently, resveratrol showed hepatorenal antioxidant, anti-inflammatory, and antiapoptotic activities as manifested by improvement in the antioxidant markers along with a decline in NF-κB, TNF-α, and caspase-3 expressions. In conclusion, this study demonstrates a potential therapeutic role of resveratrol in mitigating diclofenac-induced hepatorenal insult, possibly via modulating miR-144/Nrf2/ GSH axis.