The role and mechanism of TGF-β1 in the antidepressant-like effects of tetrahydrocurcumin

Astrocytes and the activation of inflammatory factors are associated with depression. Tetrahydrocurcumin (THC), the principal metabolite of natural curcumin, is renowned for its anti-inflammatory properties. In this research, we explored the impact of THC on the expression of inflammatory factors, neurotrophins, and transforming growth factor beta 1 (TGF-beta 1) in the prefrontal cortex after chronic restraint stress (CRS) in mice and in lipopolysaccharide (LPS)-induced TNC1 astrocytes. Our findings indicated that THC mitigated the anxiety and depression-like behaviours observed in CRS mice. It also influenced the expression of TGF-beta 1, p-SMAD3/SMAD3, sirtuin 1 (SIRT1), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), inducible nitric oxide synthase (iNOS), and tumour necrosis factor alpha (TNF-alpha). Specifically, THC augmented the expressions of TGF-beta 1, p-SMAD3/SMAD3, SIRT1, BDNF, and GDNF, whilst diminishing the expressions of iNOS and TNF-alpha in LPS-induced astrocytes. However, when pre-treated with SB431542, a TGF-beta 1 receptor inhibitor, it nullified the aforementioned effects of THC on astrocytes. Our results propose that THC delivers its anti-depressive effects through the activation of TGF-beta 1, enhancement of p-SMAD3/SMAD3 and SIRT1 expression, upregulation of BDNF and GDNF, and downregulation of iNOS and TNF-alpha. This research furnishes new perspectives on the anti-inflammatory mechanism that underpins the antidepressant-like impact of THC.

Automated summary

This study explores the anti-inflammatory mechanism and antidepressant effects of THC by modulating the expression of various factors in astrocytes, providing new insights into the therapeutic potential of THC for depression.