Amyloid-β peptide (Aβ) induced cholinergic system and mitochondrial dysfunction are major risk factors for Alzheimer's disease (AD). Our previous studies found that carnosic acid (CA), an important polyphenols antioxidant, could...

Neurodegenerative diseases (NDs) such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease are incurable diseases with progressive loss of neural function and require urgent development of effective treatments. Carnosol (CL) reportedly has a pharmacological effect in the prevention of dementia. Nevertheless, the mechanisms of CL’s neuroprotection are not entirely clear. The present study aimed to investigate the effects and mechanisms of CL-mediated neuroprotection through Caenorhabditis elegans models. First, CL restored ND protein homeostasis via inhibiting the IIS pathway, regulating MAPK signaling, and simultaneously activating molecular chaperone, thus inhibiting amyloid peptide (Aβ), polyglutamine (polyQ), and α-synuclein (α-syn) deposition and reducing protein disruption-mediated behavioral and cognitive impairments as well as neuronal damages. Furthermore, CL could repair mitochondrial structural damage via improving the mitochondrial membrane protein function and mitochondrial structural homeostasis and improve mitochondrial functional defects via increasing adenosine triphosphate contents, mitochondrial membrane potential, and reactive oxygen species levels, suggesting that CL could improve the ubiquitous mitochondrial defects in NDs. More importantly, we found that CL activated mitochondrial kinetic homeostasis related genes to improve the mitochondrial homeostasis and dysfunction in NDs. Meanwhile, CL up-regulated unc-17, cho-1, and cha-1 genes to alleviate Aβ-mediated cholinergic neurological disorders and activated Notch signaling and the Wnt pathway to diminish polyQ- and α-syn-induced ASH neurons as well as dopaminergic neuron damages. Overall, our study clarified the beneficial anti-ND neuroprotective effects of CL in different aspects and provided new insights into developing CL into products with preventive and therapeutic effects on NDs.

Many litchi flowers are discarded in China every year. The litchi flower is rich in volatile compounds and exhibits strong anti-obesity activity. Litchi flower essential oil (LFEO) was extracted by the continuous phase transformation device (CPTD) independently developed by our research group to recycle the precious material resources in litchi flowers. However, its fat-reducing effect and mechanism remain unclear. Employing Caenorhabditis elegans as a model, we found that LFEO significantly reduced fat storage and triglyceride (TG) content in normal, glucose-feeding, and high-fat conditions. LFEO significantly reduced body width in worms and significantly decreased both the size and number of lipid droplets in ZXW618. LFEO treatment did not affect energy intake but increased energy consumption by enhancing the average speed of worms. Further, LFEO might balance the fat metabolism in worms by regulating the DAF-2/IIS, sbp-1/mdt-15, and nhr-49/mdt-15 pathways. Moreover, LFEO might inhibit the expression of the acs-2 gene through nhr-49 and reduce β-oxidation activity. Our study presents new insights into the role of LFEO in alleviating fat accumulation and provides references for the large-scale production of LFEO to promote the development of the litchi circular economy.