Background Diabetes mellitus (DM) is a well-known clinical entity with various late complications. There is a surge of research aiming to use the medical herb in the management of DM. Objective This study aimed to investigate whether the alleviation of DM by an isolated compound from Rosa canina is mediated by DNA methylation in STZ-diabetic rats. Methods Sixty adult Wistar male rats were classified into control, diabetic and treatment groups. Rats were treated with STZ (40 mg/kg), metformin (500 mg/kg), and oligosaccharide fraction (OF; 10, 20 and 30 mg/kg) isolated from Rosa canina. DNA was extracted from the blood and pancreas to determine DNA methylation using the Global DNA Methylation kit. The expressions of DNA methyltransferases (Dnmts), PDX1, Ins1, GCK and PTP1B2 were determined by using qRT-PCR. Results The significant blood glucose-lowering potential of OF was associated with a reduced level of global DNA methylation (p < 0.05). The expression levels of Dnmts 1 and 3α increased in the pancreas and blood from diabetic rats compared to control group which declined by OF treatment (p < 0.05). Paradoxically, the expression of Dnmt 3β augmented in the pancreas and blood of OF group compared to diabetic ones (p < 0.05). Besides, the expressions of Pdx1, PTP1B2, Ins1 and GCK increased in OF-treated rats compared to diabetic groups. Conclusion Results revealed that DNA methylation plays a causal role in the effectiveness of the isolated OF. Furthermore, the possible regenerative potential of oligosaccharide in diabetic rats may have contributed to the modulation of DNA methylation. Graphical abstract

Rutin (Rut) has been identified as a neuroprotective compound with displayed beneficial effects in Alzheimer’s disease. However, low bioavailability and solubility are the major concerns pertaining to the use of Rut. Aberrant function of autophagy has been found as a well‐established participant in the pathogenesis of neuronal degeneration. In the present study, Rut and Rut‐loaded solid lipid nanoparticles (Rut‐SLNs) were used to protect rat PC12 cells against streptozotocin‐ (STZ‐) induced neurotoxicity. Rut‐SLNs were fabricated by a solvent evaporation‐ultrasonic method. Depending on the experimental patterns including pretreatment, cotreatment, and posttreatment, PC12 cells were exposed to STZ and desired doses of the SLNs, Rut, and Rut‐SLNs. The viability of the cells, the mitochondrial membrane potential (MMP), and the expression of miR‐21, miR‐22, Akt, ATG5, Beclin1, and LC3 were evaluated by using MTT assay, rhodamine 123 fluorescent dye, and qRT‐PCR, respectively. SLN and Rut‐SLNs possess the smooth surface with an average size of 117.2 and 176.9 nm, respectively, with a negative zeta potential. The encapsulation efficiency and loading capacity of Rut in SLNs were 90.32% and 49.1%, respectively. The nanoformulation revealed a sustained drug release in vitro up to 72 h and followed Higuchi kinetics. Rut‐SLNs displayed a neuroprotective effect by augmenting the viability of PC12 cells and increasing MMP. In addition, Rut‐SLNs suppressed autophagy which was stimulated by STZ whereas, the free Rut demonstrated lower effect. Taken together, these results clearly indicated that Rut‐SLNs could be a good candidate for the prevention of neurodegenerative diseases.

Background: Diabetes is a major global health concern, manifesting the symptoms of chronic hyperglycemia. Either insufficient or excessive angiogenesis is generally involved in the pathogenesis of diabetes and its complications.Objective: Given that macronutrients are important dietary players in global health issues, we aimed to review the role of macronutrients, including carbohydrates and proteins, to manage diabetes via angiogenesis modulation.Methods: Sixteen studies regarding the effects of macronutrients, including carbohydrates and proteins derived from plants, fungus, bacteria, and their derivatives, on angiogenesis in diabetes were included in our study.Results: Reviewing these studies suggests that carbohydrates, including low molecular weight fucoidan (LMWF), Astragalus polysaccharide (APS), and Ganoderma lucidum polysaccharide (Gl-PS), as well as oligopeptides, like sea cucumber-isolated small molecule oligopeptides (SCCOPs), can induce angiogenesis in the process of wound healing. Considering retinopathy, carbohydrates, including Diphlorethohydroxycarmalol (DPHC), Lyciumbarbarum (LBP), Sulfated K5 Escherichia coli polysaccharide (K5-N, OS (H)), and carnosine suppressed retinal angiogenesis. Furthermore, rice bran protein (RBP) ameliorated angiogenesis in diabetic nephropathy. Carbohydrates, including DPHC, Anoectochilus roxburghii polysaccharide (ARP), and LMWF, showed beneficial effects on endothelial cell dysfunction.Conclusion: In conclusion, data suggest that a number of macronutrients, including proteins and carbohydrates, could have protective effects against complications of diabetes via modulation of angiogenesis.