The Medicinal Components Of Lavender And The Mechanism Of Antioxidant-based Mechanism

Alzheimer's disease(AD)is one of the most common neurodegenerative disease,which could lead to cognitive deficits,personality changes and motive dysfunction.Evidences have indicated that oxidative stress plays a key role in AD pathogenesis.The A?aggregation and oxidative stress induce and promote each other and the ROS overproduction make mitochondrial dysfunction,leading to apoptosis.At the same time,nuclear factor-erythroid 2-related factor 2(Nrf2)-heme oxygenase-1(HO-1)pathway is important in the antioxidive neuroprotection.Therefore,oxidative stress is attracting more attention in AD research,and it has treated as an important strategy for prevention and treatment of AD to find active antioxidant components from traditional herbal medicine.Lavender(Lavandula angustifolia Mill.)as a traditional Chinese medicine,has been used to treat anxiety,insomnia,depression,convulsion,pain and cerebrovascular diseases.Lavender essential oil(LO)and water extract(LE)both were reported to possess various biological activities in central nervous system and obvious antioxidant activity.(-)-Linalool(LI),as the major component,shows antioxidant effect depending on Nrf2-HO-1 pathway.Therefore,we deduced that lavender could improve the cognitive deficits in AD.In this thesis,we used various AD models in vivo and in vitro to evaluate the improvement effect of the components in lavender,then explored the related mechanism.Moreover,to make sure the safe use of lavender oil,especially on the center nervous system,the changes of neurobehaviors,especially the motive function of normal animals were evaluated and the related mechanism was explored further.The main research findings were as follows:1.The cognitive improvement effect of active components in lavenderThe neuroprotective and cognitive improvement effect of LO and LE were evaluated and compared firstly.PC 12 cell injury models induced by H2O2 and A?25-35 and animal model induced by scopolamine were used to evaluate the activities of LO and LE.The results showed that LO possessed significant neuroprotective effects on cell injuries and cognitive improving effects in mice,while LE showed no significant effect.Thus,we further focused on the effects of LO.First,the chemical constitution of LO was determined using a GC-MS method,which showed LI is its main component(37.96%).Then,the improvement effects of LO and LI on cognitive deficits in AD mice were researched.The A?1-40 intrahippocampal microinjection induced or D-galactose(D-gal)and AlCl3 induced AD mice were established,the results of Morris water maze test and step though test were showed that LO and LI could improve the cognitive deficits in those AD mice,moreover,the LI had better effect compared with the same dose LO.2.The neuroprotection of LO and LI based on their anti-oxidative activityIn study in vivo,the hippocampus of A?1-40 induced AD mice were undertook the biochemical analysis,western blot test and TUNEL staining,the results showed that LO and LI could reverse the SOD,GPX activity and MDA level,and inhibit caspase activation,MMP damage and apoptosis in model mice.Meanwhile,in the D-galactose(D-gal)and AlCl3 treated mice,LO and LI also showed anti-oxidative effect in the hippocampus,and they elevated the expression of synaptic plasticity related proteins including CaMK?,p-CaMK?,BDNF and TrkB.Besides,using the PC12 cell injury models induced by H2O2 and A?25-35,we also found the LO and LI reversed the ROS,NO,cleavedcaspase proteins,MMP and apoptosis rate in model cells.Therefore,LO and LI have obvious anti-oxidative and anti-apoptosis effect contributing to their neuroprotection.We further researched the role of Nrf2-HO-1 pathway in the neuroprotection of LI against oxidative damage.PC 12 cells were incubated with LI directly,and analyzed by western blots test.The results showed that LI could induce HO-1,Nrf2 protein expression and Akt activation in a dose-dependent and time-dependent manner.When the PI3K/Akt inhibitor LY249002 or HO-1 inhibitor ZnPP were pre-incubated with cells,the elevated HO-1 expression induced LI was inhibited and neuroprotective effect of LI was reduced significantly.Besides,LI induces HO-1 and Nrf2 expression in the hippocampus of AD model mice induced by A?1-40 and D-gal+AlCl3.Therefore,LI improves oxidative insults might though upregulating Nrf2-HO-1 pathway.3.The influence of LO on the neurobehavior of normal miceThough the evaluation of different behavioral test,LO showed little effect on cognitive and emotional behavior of normal mice,but it inhibited their movement.Then the particular research about motor function showed that LO could inhibit the motor activity and improve motor coordination obviously,no matter in one-dose or multi-dose administration mode.This effect was dose-dependent and the low-dose LO would not influence the movement of normal mice.It made sure the safe use of LO.The related mechanism might be related to the dopaminergic neural system and level of serotonin.In summary,our study demonstrated LO showed better neuroprotective and cognitive effects than LE,and it is the main active part of lavender.Moreover,LO and its main components LI could improve the cognitive deficits in mice induced by A?1-40 or D-gal+AlCl3,and protect the cell damages induced by H2O2 or A?25-35.Those effects might be mediated by PI3K/Akt-Nrf2-HO-1 pathway.Besides,LO could inhibit the motive activity of normal mice,but improve their motor coordination,which might related to its influence on dopamine system.Our study provide scientific basis for developing the active components of lavender into the potential drug in AD prevention and treatment.