Ethanol Extract of Centipeda minima Exerts Antioxidant and Neuroprotective Effects via Activation of the Nrf2 Signaling Pathway.

Oxidative stress is implicated in the pathogenesis of neurodegeneration and other aging-related diseases. Previous studies have found that the whole herb of Centipeda minima has remarkable antioxidant activities. However, there have been no reports on the neuroprotective effects of C. minima, and the underlying mechanism of its antioxidant properties is unclear. Here, we examined the underlying mechanism of the antioxidant activities of the ethanol extract of C. minima (ECM) both in vivo and in vitro and found that ECM treatment attenuated glutamate and tert-butyl hydroperoxide (tBHP)-induced neuronal death, reactive oxygen species (ROS) production, and mitochondria dysfunction. tBHP-induced phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinases (JNK) was reduced by ECM, and ECM sustained phosphorylation level of extracellular signal regulated kinase (ERK) in SH-SY5Y and PC12 cells. Moreover, ECM induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the upregulation of phase II detoxification enzymes, including heme oxygenase-1 (HO-1), superoxide dismutase-2 (SOD2), and NAD(P)H quinone oxidoreductase-1 (NQO-1) in both two cell types. In a D-galactose (D-gal) and aluminum muriate (AlCl3)-induced neurodegenerative mouse model, administration of ECM improved the learning and memory of mice in the Morris water maze test and ameliorated the effects of neurodegenerative disorders. ECM sustained the expression level of postsynaptic density 95 (PSD95) and synaptophysin (SYN), activated the Nrf2 signaling pathway, and restored the levels of cellular antioxidants in the hippocampus of mice. In addition, four sesquiterpenoids were isolated from C. minima to identify the bioactive components responsible for the antioxidant activity of C. minima; 6-O-angeloylplenolin and arnicolide D were found to be the active compounds responsible for the activation of the Nrf2 signaling pathway and inhibition of ROS production. Our study examined the mechanism of C. minima and its active components in the amelioration of oxidative stress, which holds the promise for the treatment of neurodegenerative disease.

Berberine Improves Diabetic Encephalopathy Through the SIRT1/ER Stress Pathway in db/db Mice.

The association between diabetes and dementia has been well demonstrated by epidemiologic studies. Berberine (BBR) has been reported to ameliorate diabetes and diabetic encephalopathy (DE). However, the mechanism is still unknown. In this study, we employ a diabetic model, db/db mice, to explore whether BBR could protect DE through the SIRT1/endoplasmic reticulum (ER) stress pathway. Behavioral results (Morris water maze, Y-maze spontaneous alternation test, and fear conditioning test) showed that oral administration of BBR (50 mg/kg) improved the learning and memory ability. Furthermore, BBR promoted lipid metabolism and decreased fasting glucose in db/db mice. Moreover, western blot analysis revealed that BBR increased the synapse- and nerve-related protein expression (PSD95, SYN, and NGF) and decreased the protein expression of inflammatory factors (TNF-α and NF-κB) in the hippocampus of db/db mice. BBR also increased the protein expression of SIRT1 and downregulated ER stress-associated proteins (PERK, IRE-1α, eIF-2α, PDI, and CHOP) in the hippocampus of db/db mice. Taken together, the present results suggest that the SIRT1/ER stress pathway might be a crucial mechanism in the neuroprotective effect of BBR against DE.