Therapeutical Effect Of Rose Essential Oil From Chinese Kushui Rose (Rosa Setate×Rosa Rugosa) In AD C.elegans And Its Mode Of Action

Alzheimer's disease(AD)is the most common neurodegenerative disease associated old people in the world,it has caused unbearable burden to both the affected family and society.For that reason,many researches have focused on discovering and developing more effective therapeutic medications for treating AD.Previous work reported that,the Rosa damascene essential oil possesses a significant antioxidant activity,and it can remarkably inhibit the activity of acetylcholin esterase and butyrylcholine esterase in vitro.Also,it can dramatically improve learning and memory impairment in AD rat.These results indicate that the rose essential oil might be potential to fight against AD.In this study,the therapeutical effects of rose essential oil from Chinese Kushui rose(Rosa setate×Rosa rugosa)for treating AD were explored,and its mode of action was investigated by using transgenic C.elegans with human A?1-42 as AD model.The transgenic C.elegans of CL4176 can overexpress human A?1-42 peptides in their body wall muscle cells,thus leading to AD-like symptom of paralysis phenotype.After treatment with rose essential oil,the AD-like symptoms of CL4176 worms were significantly inhibited in a dose-dependent manner.Whereas,the inhibitory effects of citronellol and geraniol,the main components of the rose essential oil,on paralysis phenotype were inferior to the oil itself.Another transgenic C.elegans of CL2355 can overexpress human A?1-42 peptides in the nerve cells,and then,the worms display hypersensitive to exogenous 5-HT.As expected,the AD-like symptom of hypersensivity to exogenous 5-HT due to A? toxicity has been significantly reverted after rose essential oil treatment.These results gave us a notion that the rose essential oil acted effectively for treating AD worms.The transgenic worms of CL2006 can simulate the progressive process of AD due to constitutively expressing human A?1-42 peptides in their muscle cells.Further study showed that rose essential oil significantly suppressed A? deposits in these CL2006 worms.After knocking down the expressions of skn-1,daf-16 and hsf-1 genes by RNAi,the inhibitory effects of rose essential oil on worm paralysis phenotype were abrogated only after skn-1 RNAi,but not after daf-16 RNAi and hsf-1 RNAi.Additionally,rose essential oil markedly activated SKN-1 nuclear localization,and upregulated the expression of gst-4 gene downstream target of skn-1.Finally,the result of western blot showed that rose essential oil reduced the level of higher toxic A? oligomers to alleviate the A?-induced damages on organisms in C.elegans.Taken together,the results in present work indicated that the SKN-1 signaling pathway was involved in the therapeutical effect of rose essential oil on AD C.elegans.Our results will provide powerful data information and theoretical foundation for reshaping medicinal products of rose essential oil from Chinese Kushui rose(Rosa setate×Rosa rugosa)in the future.