Role of Nrf2/HO-1 signaling pathway in treatment of schizophrenia rats with paliperidone was written by Wang, Li;Zhang, Song;Long, Wei. And the article was included in Zhongguo Laonianxue Zazhi in 2022.COA of Formula: C23H27FN4O3 This article mentions the following:
Objective: To investigate the mechanism of NF-E2-related factor (Nrf)2/heme oxygenase (HO)-1 signaling pathway in the treatment of schizophrenia (SZ) rats with paliperidone. Methods: Fifty SPF SD rats were randomly divided into 5 groups: control group (Control group), SZ group (Model group), risperidone group, low-dose paliperidone group and high-dose paliperidone group. The rat model of SZ development was established by i.p. injection of didroxepine maleate (MK-801, 0.25 mg/kg). Rats in low-dose paliperidone group, high-dose paliperidone group and risperidone group were given paliperidone (0.03 mg/kg, once daily), paliperidone (0.30 mg/kg, once daily) and risperidone (0.10), resp. mg/kg, once a day), and rats in Control group and Model group were given the same amount of normal saline. The open field test box was used to analyze the changes of total distance within 10 min in each group. Morris water maze was used to test the reference memory of rats in each group. Social interaction test box was used to test the social interaction ability of rats in each group. And Western blotting was used to detect the expression levels of Caspase-3, Bax protein, Nrf2 and HO-1 in hippocampus tissues of rats in each group. Results: Compared with the Control group, the total distance of spontaneous activity in the Model group was significantly increased, the escape latency was significantly increased, the frequency of crossing the platform was significantly decreased, and the social interaction time and the percentage of non-aggressive behavior were significantly decreased (P<0.05). Compared with the Model group, the total distance of spontaneous activity in risperidone group, the low-dose paliperidone group and the high-dose paliperidone group were significantly decreased, the escape latency was significantly decreased, the number of platform crossing was significantly increased, the social interaction time and the percentage of non-aggressive behavior were significantly increased (P<0.05). Compared with the Control group, the expression levels of caspas-3 and Bax protein in the Model group were significantly increased, and the expression levels of Nrf2 and HO-1 protein were significantly decreased (P<0.05). Compared with the Model group, the protein expression levels of digested caspase-3 and Bax in the hippocampus of risperidone group, low-dose paliperidone group and high-dose paliperidone group were significantly decreased, and the protein expression levels of Nrf2 and HO-1 were significantly increased (P<0.05). Conclusion: Paliperidone can alleviate abnormal behavior in SZ model rats, and may play a role by regulating Nrf2/HO-1 signaling pathway. In the experiment, the researchers used many compounds, for example, 3-(2-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (cas: 144598-75-4COA of Formula: C23H27FN4O3).
3-(2-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (cas: 144598-75-4) belongs to isoxazole derivatives. Isoxazoles are aromatic heterocycles containing an N–O bond. The weakness of this bond allows the ring opening of these heterocycles under reductive conditions. As with isoxazolines, isoxazoles may be cleaved using low-valent titanium obtained from the Kulinkovich reaction.This procedure affords enaminoketones from 2,4-substituted isoxazoles.COA of Formula: C23H27FN4O3
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem