The Chinese medicine formula Shexiang baoxin pill and the natural compound berberine alleviate cognitive impairment and depressive disorders : insights into neuroinflammatory and neuroplasticity

Abstract

Depression has risen as a serious global issue that affects the public health of all ages. Due to the pathogenesis of depression is still not well understood, current antidepressants are not satisfactory in terms of effectiveness especially when the symptoms vary. Depression is often associated with cognitive impairment; however, currently little attention was paid to cognitive disorders associated with depression and few medications for the condition have been developed in the past years.

Shexiang Baoxin Pill (SBP), a multi-component formula drive from Traditional Chinese Medicine (TCM), has shown potential effects for neuropsychiatric disorders. However, the mechanism of SBP for neuroprotection during and after stroke is insufficient. Post-stroke cognitive impairment (PSCI) occurs frequently among stroke survivors with depression. Herein, studies combined network pharmacology approach with in vivo and in vitro experimental validation to explore the effects of SBP for PSCI induced by the middle cerebral artery occlusion (MCAO) in rats were performed. The in vitro experiment results suggested that SBP enhanced neuronal cells viability and downregulated neural apoptosis in neuronal cells via activating the PI3K/Akt signaling pathway. Next, in vivo experiment results illustrate that SBP treatment attenuates the brain injury after stroke in the acute MCAO rats. In behavioral tests of chronic MCAO rats, SBP attenuates the cognitive impairment and depressive- and anxiety-like behaviors. Additionally, SBP regulates the production of synaptic proteins NMDAR1, CaMKII, PSD-95, and AMPAR, which inhibited by MCAO injury. These results indicated that SBP treatment might be a potential option for PSCI.

Coptis Rhizoma (Huanglian) is widely used in a series of TCM formulas for regulating emotional disorders. There is renewed interest in berberine, the main bioactive compound extract for Coptis Chinensis, which is well-established for its promoting inflammation in neurodegenerative and neuropsychiatric disorders. In the current study, we found that berberine decreases neuroinflammation and improves synaptic plasticity and behavioral patterns via inhibiting NLRP3 inflammasome activation. Herein, we designed this study to assess the anti-depressive effect of berberine using both lipopolysaccharide (LPS) and corticosterone-induced (CORT) depression mice model. The results showed that berberine could reserve the depression- and anxiety-like behavior induced by LPS and CORT. Then, differentially expressed gene analysis of RNA sequencing data from the prefrontal cortex to identify a hub gene that is responsible for inflammation, neuroplasticity, and steroid biosynthesis. Long-term CORT administration resulted in excitatory synaptic dysfunction and depressive behavior in mice, whereas berberine modified excitatory synaptic function and depressive behavior. Additionally, berberine significantly reversed the peripheral and brain pro-inflammatory cytokines and neuroinflammation by inhibiting NLRP3 inflammasome-mediated signaling pathway activation. Berberine reversed the hippocampal adult neurogenesis and neuroplasticity defects induced by CORT. Our findings provide novel evidence that berberine may be a potential therapeutic option for depression in the future.

In conclusion, current study identified the new functions of SBP as a formula and berberine as a bioactive compound for the neuropsychiatric disorders. Moreover, this study also found that NLRP3 can be applied as the drug target for depression in terms of promotion of neurogenesis and protective effects against emotional deficits induced by depression.