Salvianolic acid B protects against lipopolysaccharide-induced behavioral deficits and neuroinflammatory response: involvement of autophagy and NLRP3 inflammasome.
BACKGROUND
The NLRP3 inflammasome activation and neuroinflammation are known to be involved in the pathology of depression, whereas autophagy has multiple effects on immunity, which is partly mediated by the regulation of inflammasome and clearance of proinflammatory cytokines. Given the emerging evidence that autophagy dysfunction plays an essential role in depression, it is very likely that autophagy may interact with the inflammatory process in the development and treatment of depression. Salvianolic acid B (SalB), a naturally occurring compound extracted from Salvia miltiorrhiza, contains anti-inflammatory and antidepression properties and has recently been proven to modulate autophagy. In this study, we sought to investigate whether autophagy is involved in the inflammation-induced depression and the antidepressant effects of SalB.


METHODS
The effects of prolonged lipopolysaccharide (LPS) treatment and SalB administration on behavioral changes, neuroinflammation, autophagic markers and NLRP3 activation in rat hippocampus were determined by using behavioral tests, real-time PCR analysis, western blot, and immunostaining.


RESULTS
Our data showed that periphery immune challenge by LPS for 2 weeks successfully induced the rats to a depression-like state, accompanied with enhanced expression of pro-inflammatory cytokines and NLRP3 inflammasome activation. Interestingly, autophagic markers, including Beclin-1, and the ratio of LC3II to LC3I were suppressed following prolonged LPS exposure. Meanwhile, co-treatment with SalB showed robust antidepressant effects and ameliorated the LPS-induced neuroinflammation. Additionally, SalB restored the compromised autophagy and overactivated NLRP3 inflammasome in LPS-treated rats.


CONCLUSIONS
Collectively, these data suggest that autophagy may interact with NLRP3 activation to contribute to the development of depression, whereas SalB can promote autophagy and induce the clearance of NLRP3, thereby resulting in neuroprotective and antidepressant actions.
['Jiang|Pei|P|', 'Guo|Yujin|Y|', 'Dang|Ruili|R|', 'Yang|Mengqi|M|', 'Liao|Dehua|D|', 'Li|Huande|H|', 'Sun|Zhen|Z|', 'Feng|Qingyan|Q|', 'Xu|Pengfei|P|']
D000818:Animals D000893:Anti-Inflammatory Agents D001343:Autophagy D001522:Behavior, Animal D001572:Benzofurans D003863:Depression D058847:Inflammasomes D007249:Inflammation D008070:Lipopolysaccharides D008297:Male D000071199:NLR Family, Pyrin Domain-Containing 3 Protein D051381:Rats D017207:Rats, Sprague-Dawley
Salvianolic acid B Autophagy NLRP3 Neuroinflammation Depression