Vitamin E plays an important role in attenuating muscle damage caused by oxidative stress and inflammation. Despites of beneficial effects from antioxidant supplementation, effects of antioxidants on exercise-induced muscle damage are still unclear. The aim of this meta-analysis was to investigate the effects of dietary vitamin E supplementation on exercise-induced muscle damage, oxidative stress, and inflammation in randomized controlled trials (RCTs). The literature search was conducted through PubMed, Medline, Science Direct, Scopus, SPORTDiscuss, EBSCO, Google Scholar database up to February 2022. A total of 44 RCTs were selected, quality was assessed according to the Cochrane collaboration risk of bias tool (CCRBT), and they were analyzed by Revman 5.3. Dietary vitamin E supplementation had a protective effect on muscle damage represented by creatine kinase (CK; SMD −1.00, 95% CI: −1.95, −0.06) and lactate dehydrogenase (SMD −1.80, 95% CI: −3.21, −0.39). Muscle damage was more reduced when CK was measured immediately after exercise (SMD −1.89, 95% CI: −3.39, −0.39) and subjects were athletes (SMD −5.15, 95% CI: −9.92, −0.39). Especially vitamin E supplementation lower than 500 IU had more beneficial effects on exercise-induced muscle damage as measured by CK (SMD −1.94, 95% CI: −2.99, −0.89). In conclusion, dietary vitamin E supplementation lower than 500 IU could prevent exercise-induced muscle damage and had greater impact on athletes

Alzheimer's disease (AD) is the most common dementia characterized by the excessive accumulation of amyloid-beta (Aβ) and tau aggregates, as well as neuronal damage and neuroinflammation. Metabolic disruption in AD has been noticed because metabolite alterations closely correlate with Aβ neuropathology and behavioral phenotypes. Accordingly, controlling various neuropathological processes and metabolic disruption is an efficient therapeutic strategy for AD treatment. In this study, we evaluated the effects of a combination of Cuscuta seeds and Lactobacillus paracasei NK112 (CCL01) on AD neuropathology and altered metabolism in five familial AD (5xFAD) transgenic mice and neuronal cell cultures. First, we observed that CCL01 exerted neuroprotective effects in HT22 hippocampal neurons and primary cultured neurons. CCL01 ameliorated memory decline and protected synapses and neuronal survival in 5xFAD mice. These effects were related to the inhibition of tau phosphorylation. CCL01 also inhibited the activation of mitogen-activated protein kinase (MAPK) signaling and neuroinflammatory processes. Moreover, the metabolite profile-particularly characterized by altered phospholipid metabolism-was significantly changed in the 5xFAD group, while CCL01 partly restored the alteration. Lysophosphatidylcholine (lysoPC), the levels of which were higher in the brains of 5xFAD mice, exerted neurotoxicity in vitro, whereas CCL01 protected neurons from lysoPC-induced toxicity by regulating MAPK signaling. Additionally, CCL01 administration reduced gut inflammation in the 5xFAD mice. In summary, we demonstrated that CCL01 improved the memory function of 5xFAD mice by protecting neurons against Aβ- and lysoPC-induced toxicity through the regulation of MAPK signaling, neuroinflammation, tau phosphorylation, and gut inflammation, suggesting the potential of CCL01 as treatment for AD.

Neuroinflammation is a crucial step involved in development and progression of Alzheimer's disease. The current study found that Petasites japonicus leaf extract inhibits neuroinflammation induced by lipopolysaccharides and amyloid beta oligomers.

Prolonged endoplasmic reticulum (ER) stress can mediate inflammatory myopathies and insulin signaling pathways. The double-stranded RNA (dsRNA)-activated protein kinase R (PKR) has been implicated in skeletal muscle dysfunction. However, pathological roles of PKR in ER stress in muscle are not fully understood. The current study aimed to investigate the effect of imoxin (IMX), a selective PKR inhibitor, on tunicamycin (TN)-induced promotion of ER stress and suppression of insulin signaling in C2C12 myotubes. Cells were pretreated with 5 µM IMX for 1 h and exposed to 0.5 µg/mL TN for 23 h. A subset of cells was stimulated with 100 nM insulin for the last 15 min. mRNA expression and protein levels involved in ER stress were measured by RT-PCR and Western blotting, respectively. TN significantly augmented PKR phosphorylation by 231%, which was prevented by IMX. In addition, IMX reduced mRNA and protein levels of ER stress-related markers, including CCAAT-enhancer-binding protein homologous protein (CHOP, mRNA: 95% decrease; protein: 98% decrease), activating transcription factor 4 (ATF4, mRNA: 69% decrease; protein: 99% decrease), cleavage of ATF6, and spliced X-box-binding protein 1 (XBP-1s, mRNA: 88% decrease; protein: 79% decrease), which were induced by TN. Furthermore, IMX ameliorated TN-induced suppression of phospho-insulin receptor β (317% increase) and Akt phosphorylation (by 36% at Ser473 and 30% at Thr308) in myotubes, while augmenting insulin-stimulated AS160 phosphorylation and glucose uptake (by ∼30%). These findings suggest that IMX may protect against TN-induced skeletal muscle ER stress and insulin resistance, which are potentially mediated by PKR.