Xiaoyao Pills Ameliorate Depression-like Behaviors and Oxidative Stress Induced by Olfactory Bulbectomy in Rats via the Activation of the PIK3CA-AKT1-NFE2L2/BDNF Signaling Pathway

• DOI: 10.3389/fphar.2021.643456
• Publication Date: 2021-04-16T03:30:01Z
• Authors: Yafei Ji; Jie Luo; Jiuseng Zeng; Yang Fang; Rong Liu; Fei Luan; Nan Zeng
• Keywords: olfactory bulbectomized rats; Pharmacology; 0303 health sciences; 03 medical and health sciences; xiaoyao pills; depression; oxidative stress; inflammatory response; Therapeutics. Pharmacology; RM1-950; 3. Good health

Numerous studies have revealed that oxidative stress is closely associated with the occurrence and development of depression. Xiaoyao Pills (XYW) are included in Chinese Pharmacopoeia frequently used for treating anxiety depression by smoothing liver, strengthening spleen, nourishing blood. However, antidepressant effects XYW not yet been thoroughly investigated. The objective our study was to investigate antidepressant-like underlying molecular mechanism olfactory bulbectomized (OB) rat model using open field test (OFT), sucrose preference (SPT), splash (ST), novelty suppressed feeding (NSFT). Results showed (0.93 1.86 g·kg −1 ) significantly alleviated depression-like behaviors rats, which indicated increased SPT, prolonged grooming time ST, decreased horizontal movement OFT, shorter latency NSFT. In addition, treatment dramatically reversed reduced activity superoxide dismutase level glutathione, while also lowering levels malondialdehyde, an inflammatory mediator (nitric oxide), pro-inflammatory cytokines (interleukin-6 1β) serum cortex OB rats. Mechanistically, induced marked upregulation mRNA protein expression NFE2L2, KEAP1, GPX3, HMOX1, SOD1, NQO1, OGG1, PIK3CA, p-AKT1/AKT1, NTRK2, BDNF, downregulation ROS hippocampus via activation NFE2L2/KEAP1, PIK3CA/AKT1, NTRK2/BDNF pathways. These findings suggest exert rats symptoms, these mediated alleviation enhancement neuroprotective through PIK3CA-AKT1-NFE2L2/BDNF signaling