Curcumin Trinicotinate Improves Synapse Formation In High-fat Diet Rats

[Background and Objective]At present,obesity has become one of the most epidemic common diseases in the world.High-fat diet(HFD) or obesity is closely related to cognitive-related neurological diseases.Studies have shown that synapse formation is the basis for the formation of cognitive function,and that HFD significantly impairs synapse formation in the brain.Curcumin is a natural food additive with various pharmacological activities such as lipid-lowering,anti-inflammatory,anti-oxidation,anti-apoptosis and so on.Curcumin Trinicotinate(CurTn) is an ester derivative that effectively combines the advantages of curcumin and nicotinic acid.It has the characteristics of safer,more pharmacological activity and higher bioavailability than curcumin.Supplementation of curcumin in the diet can significantly increase the expression of brain derived neurotrophic factor(BDNF) in mice.The BDNF/TrkB/CREB pathway is closely related to cognitive function,which can significantly improve synapse formation.Therefore,we investigated whether CurTn can improve synapse formation in HFD rats via up-regulating BDNF/TrkB/CREB pathway.[Method]After 1 week of adaptive feeding,male Wister rats were divided into 5 groups randomly,8 per group which including Control group,HFD group,HFD + 50 mg/kg/d CurTn group,HFD + 100 mg/kg/d CurTn group and HFD + 150 mg/kg/d CurTn group.Except for the control group,other groups received a one-time high-dose Vit D3 600,000 IU/Kg intraperitoneal injection on the first day which could accelerate lipid penetration.The high-fat diet consists of 1% cholesterol,5% lard and 94% normal diet.The rats were sacrificed after 8 weeks of feeding.The expressions of synaptic related proteins PSD-95,Synapsin-1,Glu R1 and BDNF/TrkB/CREB pathway-related proteins BDNF,p-TrkB,TrkB,p-CREB and CREB were detected by Western blotting.[Result] 1.CurTn improves synapse formation in HFD rats.CurTn increased the expression of synaptic related proteins PSD-95 and Synapsin-1 in HFD rats: Western blotting showed that the expression of PSD-95 and Synapsin-1 protein in HFD group was significantly lower than that in control group.The expression of PSD-95 and Synapsin-1 protein in HFD rats treated with 100 mg/kg/d or 150 mg/kg/d were significantly higher than that in HFD group.CurTn increased the expression of Glu R1 in HFD rats: Western blotting results showed that the expression of Glu R1 in HFD rats treated with CurTn(100 mg/kg/d,150 ma/kg/d)were significantly higher than that in HFD group.2.CurTn up-regulates BDNF/TrkB/CREB pathway-associated protein in HFD rats.CurTn increased the expression of BDNF/TrkB/CREB pathway-related proteins including BDNF,p-TrkB,and p-CREB in HFD rats: Western blotting results showed that the expression of BDNF,p-TrkB,and p-CREB in HFD group was significantly decreased compared with control group.The expression of BDNF,p-TrkB,and p-CREB in HFD rats treated with CurTn(100 mg/kg/d,150 mg/kg/d)were significantly higher than that in HFD group.There was no significant change in the expression of total CREB and total TrkB in brain tissue of each group.[Conclusion]CurTn improves brain synapse formation in HFD rats,and its mechanism is related to up-regulation of BDNF/TrkB/CREB pathway in brain.