The deposition of amyloid β-protein (Aβ) fibrils into plaques within the brain parenchyma and along cerebral blood vessels is a hallmark of Alzheimer's disease (AD). Aβ42 oligomers and fibrils cause the breakdown of neural circuits, neuronal death and eventually dementia. Drugs that inhibit Aβ42 aggregation may be a novel direction in AD drug discovery. Cryptotanshinone (CTS), an active component of the medicinal herb Salvia miltiorrhiza, has been shown to improve learning and memory in several pharmacological models of AD. However, the effects of CTS on the Aβ aggregation and toxicity are unclear. The current work shows the effectiveness of CTS on the inhibition of Aβ42 aggregation and toxicity to human neuroblastoma cells. In this study, we demonstrated that CTS can inhibit Aβ42 spontaneous aggregation using thioflavin T fluorescence assay and transmission electron microscopy. Furthermore, we investigated the effects of CTS on Aβ-induced oxidative cell death in cultured SH-SY5Y cells. MTT and lactate dehydrogenase assays showed that CTS reduced the cytotoxicity induced by Aβ42. CTS also dramatically reduced Aβ42-induced cellular apoptosis and increased level of reactive oxygen species in these cells. Our study suggests that CTS may be useful in the inhibition or prevention of AD development and progression.
We assessed the efficacy and safety of oral antidiabetic drugs (OADs) as an add-on treatment in patients with type 2 diabetes uncontrolled on metformin. PubMed, the Cochrane Library, and Embase were searched from inception to October 20, 2017. Pairwise and network meta-analyses were conducted using Stata 14.1 software. Odds ratios (ORs) and weighted mean differences (WMDs) were used to evaluate outcomes. Sixty-eight trials including 36,746 patients were analyzed. No significant differences in the risk of major adverse cardiovascular events (MACEs) and all-cause mortality were observed among any class of OADs when combined with metformin. All classes of OADs as add-ons to metformin improved glucose control, while sodium-glucose co-transporter-2 (SGLT-2) inhibitors showed greater fasting plasma glucose (FPG) reductions {WMD, − 1.49 [95% confidence interval (CI) − 1.69 to − 1.28] mmol/l} and 2 h postprandial glucose (2 h PPG) reductions [WMD, − 3.07 (95% CI − 4.12 to − 2.03) mmol/l]. Thiazolidinediones and sulfonylureas were associated with weight gain [WMD, 2.53 (95% CI 1.95–3.10) kg and 2.00 (95% CI 1.63–2.36) kg, respectively] when added to metformin. Sulfonylureas [WMD, 6.52 (95% CI 4.07–10.45)] were associated with the highest ORs of hypoglycemia. Our results suggest that the seven classes of OADs were not associated with any increased risk of MACEs or all-cause mortality when combined with metformin. Most OADs were associated with similarly large reductions in HbA1c levels when added to metformin, while SGLT-2 inhibitors might be the best option for reducing body weight, FPG, and 2-h PPG.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0482-5) contains supplementary material, which is available to authorized users.
Traumatic brain injury (TBI) may trigger secondary injury cascades including endoplasmic reticulum stress, oxidative stress, and neuroinflammation. Unfortunately, there are no effective treatments targeting either primary or secondary injuries that result in long-term detrimental consequences. Huperzine A (HupA) is a potent acetylcholinesterase inhibitor (AChEI) that has been used treatment of Alzheimer's disease (AD). This study aimed to explore the neuroprotective effects of HupA in TBI and its possible mechanisms. Repetitive mild closed head injury (CHI) model was used to mimic concussive TBI. Mice were randomly assigned into three groups including sham, vehicle-treated and HupA-treated injured mice. The HupA was given at dose of 1.0 mg/kg/day and was initiated 30 min after the first injury, then administered daily for a total of 30 days. The neuronal functions including motor functions, emotion-like behaviors, learning and memory were tested. Axonal injury, reactive oxygen species (ROS), and neuroinflammation were examined as well. The results showed that injured mice treated with HupA had significant improvement in Morris water maze performance compared with vehicle-treated injured mice. HupA treatment significantly attenuated markers of neuroinflammation and oxidative stress in the injured mice. Taken together, HupA was effective in reducing neuroinflammation, oxidative stress and behavioral recovery after TBI. HupA is a promising candidate for treatment of TBI.
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