| Objective: To study the potential substances in Parkinson’s disease in fruit of B.lindleyana Fort.and explore its mechanism of resistance to Parkinson’s disease,so as to provide ideas for the full utilization of B.lindleyana Fort.resources and screening of potential drugs against PD.Methods: To study effects of the mimengoside C and mixture(HHW)on the PD model of C.elegans by using the N2,NL5901 and UA57.To explore the effects of mimengoside C and HHW to nematodes lifespan,the number of offspring,athletic ability,resistant to oxidative stress and thermal stress effects,effects of dopaminergic neurons in C.elegans,α-syn protein expression and regulation of Parkinson’s disease-associated genes,to study the potential activity and mechanism of Parkinson’s disease.Results:(1)Using N2 and transgenic strain NL5901 as models to explore the effects of mimengoside C and HHW on their longevity and progeny numbers.When mimengoside C was found at 2 mg/m L,there was no significant difference in the number of offspring,and it was able to extend the lifespan of nematodes to some extent.At low concentrations,HHW had no significant effect on the lifespan and offspring numbers of nematodes,but at high concentrations it had a certain degree of damage to lifespan,reduced lifespan,and inhibited the number of nematode progeny.The results of the N2 group and the transgenic nematode NL5901 group were basically the same.(2)The effects of Miengoside C and HHW on the recovery of 6-OHDA-induced PD model motor impairment were studied by transgenic nematode UA57.Compared with the control group,it was found that levodopa in the positive drug group had a significant recovery effect on UA57 motor impairment.mimengoside C group had a significant effect at low concentrations of 0.5mg/m L and 2mg/m L,HHW had a significant recovery at 2mg/m L.(3)Oxidative stress experiments: mimengoside C had significant effects at 1mg/m L and 2 mg/m L,HHW had a significant effect at 2 mg/m L.It was speculated that mimengoside C and HHW were effective at certain concentrations.The detritus caused by oxidative stress has a certain recovery effect,that is,enhances the tolerance to oxidative stress.The results of the heat stress test showed that the levodopa has a protective effect on heat stress caused,that is,enhanced heat stress tolerance.mimengoside C and HHW have no obvious effects,indicating that it may not has the function of regulating the heat stress tolerance of C.elegans.(4)To study the protective effect of mimengoside C and HHW on6-OHDA-induced deletion of dopaminergic neurons in PD model through transgenic nematode UA57.The results showed that mimengoside C at 0.5 mg/m L and 2 mg/m L,HHW can significantly inhibit the loss of dopaminergic neuronsat 2 mg/m L,which play a protective role.(5)The results of fluorescence intensity of α-syn protein showed that mimengoside C and HHW had a certain inhibitory effect on the expression of α-syn,especially at a concentration of 2 mg/m L,which had a significant effect on 8 d and 10 d treatment.Western blot experiments further demonstrated that mimengoside C,and HHW can reduced the expression of transgenic NL5901 α-syn protein,and the effects of mimengoside C and HHW were obvious to compare with levodopa.(6)The results of q PCR experiments showed that mimengoside C mainly up-regulated genes such as HSP16.2,HSP12.6,GST-10 and MTL-1.HHW may up-regulate PINK1,LRK-1,HSP16.2 and HSP12.6 genes.Reduce the expression ofα-syn and protect the function of dopaminergic neurons.Conclusion: Mimengoside C and HHW in the fruit extract of Buddleja turfgrass can reduce the expression of α-syn protein and inhibit the loss of dopaminergic neurons,especially at a concentration of 2 mg/m L.The mechanism may be through the regulation of PINK1 and LRK-1 and HSP16.2 genes play a protective role.The experimental results show that mimengoside C and HHW may have the potential to treat Parkinson’s disease. |
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