Acupuncture does not protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced damage of dopaminergic neurons in a preclinical mouse model of Parkinson's disease.

Acupuncture treatment, a complementary and alternative medicine, is associated with a suggested neuroprotective effect in previous preclinical studies of Parkinson's disease (PD); however, results from human clinical trials have been mixed or unsuccessful. Recent systematic reviews of translational neuroprotective studies showed that the supposed efficacy is confounded by low methodological quality, particularly by a lack of randomization and concealed allocation. We sought to replicate previous experimental findings with a study design that mitigates the introduction of bias, including randomization, blinded outcome measures, sham acupuncture application, and allocation concealment by blinded neurotoxin administration. We performed 12 sessions of manual acupuncture at acupoint GB34 (yanglingquan) in mice that were administered the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxin for five consecutive days. In this animal model of PD, acupuncture treatment did not attenuate tyrosine hydroxylase-immunoreactive neuronal death, depletion of striatal dopamine levels, or reduced striatal tyrosine hydroxylase expression. Our results indicate that acupuncture is not neuroprotective against nigrostriatal loss in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of PD.

Effect of saucerneol D on melanin production in cAMP-elevated melanocytes.

Intracellular cAMP stimulates microphthalmia-associated transcription factor (MITF) induction in melanocytes through cAMP-responsive element binding protein (CREB), which plays a pivotal role in the gene expression of tyrosinase for melanin biosynthesis. In the present study, saucerneol D as a lignan constituent of Saururus chinensis (Saururaceae family) efficiently inhibited melanin production with IC(50) values of 188-297 nM in B16 melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH) or other cAMP elevators. Moreover, saucerneol D down-regulated α-MSH-induced gene expression of tyrosinase at the transcription level in B16 cells, but it did not directly inhibit the catalytic activity of cell-free tyrosinase. As to the molecular basis of hypopigmenting action, saucerneol D inhibited α-MSH-induced phosphorylation of CREB in the cells, and sequentially suppressed MITF induction. Taken together, this study provides saucerneol D down-regulated the gene expression of tyrosinase, resulting in the inhibition of cAMP-induced melanin biosynthesis, and suggests pharmacological potential of the lignan structure in skin hyperpigmentation.

Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase.

AMP-activated protein kinase (AMPK) functions as a fuel sensor in the cell and is activated when cellular energy is depleted. Here we report that alpha-lipoic acid (alpha-LA), a cofactor of mitochondrial enzymes, decreases hypothalamic AMPK activity and causes profound weight loss in rodents by reducing food intake and enhancing energy expenditure. Activation of hypothalamic AMPK reverses the effects of alpha-LA on food intake and energy expenditure. Intracerebroventricular (i.c.v.) administration of glucose decreases hypothalamic AMPK activity, whereas inhibition of intracellular glucose utilization through the administration of 2-deoxyglucose increases hypothalamic AMPK activity and food intake. The 2-deoxyglucose-induced hyperphagia is reversed by inhibiting hypothalamic AMPK. Our findings indicate that hypothalamic AMPK is important in the central regulation of food intake and energy expenditure and that alpha-LA exerts anti-obesity effects by suppressing hypothalamic AMPK activity.