Lycopene Alleviates Chronic Stress-Induced Spleen Apoptosis and Immunosuppression via Inhibiting the Notch Signaling Pathway in Rats

Chronic stress induction in immunosuppression and splenocyte apoptosis is commonly associated with increased susceptibility to various diseases. Lycopene (LYC) is a member of the carotenoid family with immune restoration and anti-apoptotic function. However, little is known about the mechanisms underlying the protective roles of LYC against spleen injury induced by chronic stress. Herein, male Wistar rats were undergoing chronic restraint stress and/or administered LYC (10 mg/kg) for 21 days. The effective model establishment was validated by open-field tests and levels of corticosterone in serum. Histopathological staining observation displayed that LYC could reduce chronic stress-induced spleen structure damage. Furthermore, LYC treatment significantly reduced the number of apoptotic-positive splenocytes caused by chronic stress via the death receptor apoptotic pathway. We detected the interleukin 4 and interferon γ levels in serum and spleen to determine the ratio of Th1 and Th2 and found that LYC can alleviate the immunosuppression induced by chronic stress. Notably, western blot and real-time polymerase chain reaction indicated that LYC can reduce the expression of the Notch-pathway-related proteins and mRNA in rats exposed to chronic stress. Further study of the potential mechanisms by adding the Notch pathway inhibitor DAPT revealed that LYC alleviates the structure damage, apoptosis, and immunosuppression caused by chronic stress via the suppression of the Notch pathway. Overall, this study presents a strong rationale to target LYC as a treatment strategy to relieve chronic stress-induced spleen injury.