Equivalence Evaluation of Venenum Bufonis and Its Potential Substitute NJ2196 against LPS-Induced Neuroinflammation in Mice

  OBJECTIVE  To evaluate the equivalence between Venenum Bufonis (Chansu) and its potential substitute NJ2196 against lipopolysaccharide (LPS)-induced neuroinflammation in mice.

  METHODS  Sixty-three SPF male ICR mice were randomly divided into control group, model group, fluoxetine group, toadstool low-dose group, toadstool high-dose group, NJ2196 low-dose group, and NJ2196 high-dose group, with 9 mice in each group. A single administration of LPS (0.83 mg · kg^-1, intraperitoneal injection) was given to each group except the control group to establish an inflammatory depression model. Fluoxetine group, Chansu low dose group, Chansu high dose group, NJ2196 low dose group and NJ2196 high dose group were given fluoxetine 30 mg · kg^-1, Chansu 30 mg · kg^-1, Chansu 90 mg · kg^-1, NJ2196 30 mg · kg^-1 and NJ2196 90 mg · kg^-1 by gavage, respectively, and the control and model group was given equal amount of saline. The cumulative immobility time of tail suspension and the cumulative immobility time of forced swimming in mice were observed; The levels of serum inflammatory factors IL-1β and TNF-α in mice were detected by ELISA; The mRNA expression levels of inflammatory factors IL-6, TNF-α and brain-derived neurotrophic factor (BDNF) in hippocampal tissues were detected by qPCR; The effects of Chansu and NJ2196 on inflammatory arachidonic acids were analyzed by high-sensitivity lipidomics.

  RESULTS  Compared with the model group, Chansu and NJ2196 significantly reduced the cumulative immobility time of tail suspension (P < 0.01) and the cumulative immobility time of forced swimming (P < 0.01), both significantly reduced the levels of inflammatory factors IL-1β and TNF-α in mouse serum (P < 0.01), and markedly decreased the expression of inflammatory factors IL-6 and TNF-α mRNA (P < 0.01) as well as BDNF mRNA expression (P < 0.01) in mouse hippocampus. High-sensitivity lipidomic analysis showed that the changes in inflammatory factors might be related to the downregulation of inflammatory mediators from the cyclooxygenase (COX) pathway. There was no significant difference (P>0.05) between Chansu and NJ2196 in all dose groups.

  CONCLUSION  Chansu and its potential substitute NJ2196 have significant anti-inflammatory depressive activities, and also have equivalence in the LPS-induced neuroinflammation model.