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Purpose: Pennyroyal is a species of the Lamiaceae family with potent anti-cancer and antioxidant properties. Combining this antioxidant with chemotherapeutic agents enhances the effectiveness of these agents by inducing more apoptosis in cancerous cells. Methods: Here, methotrexate (MTX) combined with Pennyroyal oil based on PEGylated nanostructured lipid carriers (NLCs) was assessed. These nanoparticles were physiochemically characterized, and their anti-cancer effects and targeting efficiency were investigated on the folate receptor-positive human breast cancer cell line (MCF-7) and negative human alveolar basal epithelial cells (A549).Results: Results showed a mean size of 97.4 ± 12.1 nm for non-targeted PEGylated NLCs and 220.4 ± 11.4 nm for targeted PEGylated NLCs, with an almost small size distribution assessed by TEM imaging. Furthermore, in vitro molecular anti-cancer activity investigations showed that Pennyroyal-NLCs and Pennyroyal-NLCs/MTX activate the apoptosis and autophagy pathway by changing their related mRNA expression levels. Furthermore, in vitro cellular studies showed that these changes in the level of gene expression could lead to a rise in apoptosis rate from 15.6 ± 8.1 to 25.0 ± 3.2 (p<0.05) for the MCF-7 cells treated with Pennyroyal-NLCs and Pennyroyal-NLCs/MTX, respectively. Autophagy and reactive oxygen species cellular evaluation indicated that treating the cells with Pennyroyal-NLCs and Pennyroyal-NLCs/MTX could significantly increase their intensity in these cells. Conclusion: Our results present a new NLCs-based approach to enhance the delivery of Pennyroyal and MTX to cancerous breast tissues.

Objectives: Tissue levels of cytokines represent of inflammation and forewarning of injury. In diabetic patients, these factors increase notably but don’t designate source of them. Retinopathy is one of the complications of diabetes mellitus that probably generates by reason of inflammatory damage in micro vascular or in retinal cells. Exercise decreases blood sugar and diabetic injurious. Investigation of IL-1 and TNF-a in retina in diabetic model rats and exercise effects on them were purposed of this study. Materials and Methods: In this experimental study, 40 adult Wistar male rats (250 ± 50 g) were used. They were randomly divided into four groups (n = 10): (1) Sedentary control (SC) group, (2) sedentary diabetic (SD) group, (3) 8-week healthy exercised (8HE) group and (4) 8-week diabetic exercised (8DE) group. A week after induction of diabetes by injection of streptozotocin, 60 min treadmill exercise and 5 days a week with 22 (m/min) speeds were undertaken. All groups were evaluated in terms of retina and optic nerve tissue levels of TNF-α and IL-1 using ELISA. Results: Based on the results, TNF- α tissue levels were decreased in the 8HE and increased in the 8DE groups compared to control, respectively. Also, no difference was observed in IL-1 tissue levels between exercised and control groups. Conclusion: Long term exercise protocol was useful in healthy rats but don’t decrease of pro-inflammatory retinal complication in diabetes mellitus.