Anti-Depressive Effectiveness of Baicalin In Vitro and In Vivo

Abstract

Baicalin (BA), a major polyphenol compound isolated from the extracts of Scutellaria radix, has been previously reported to ameliorate depressive-like behaviors in mice with chronic unpredictable mild stress (CUMS). However, its underlying antidepressant mechanisms remain unclear. This study was designed to confirm the antidepressant-like effects of BA on CUMS induced behavioral abnormalities in mice, and sought to explore the pharmacological mechanisms in vivo and in vitro. The CUMS procedure was carried out to induce depression in mice. Afterwards, the tail suspension test (TST), forced swim test (FST), and open field test (OFT) were performed within 24 h, then sucrose preference test (SPT) was conducted. Additionally, PC12 cells were pretreated with BA for 2 h, then further stimulated with corticosterone for 24 h. The levels of Interleukin-1β (IL-1β), IL-6 and Tumor Necrosis Factor-α (TNF-α) in serum, hippocampus homogenate and cell culture medium were determined using the enzyme-linked immunosorbent assay (ELISA) method. The protein expressions of inhibition of high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathways in hippocampus and PC12 cells were detected. Our results showed that CUMS-treated mice presented notable depressive-like symptoms, such as decreased sucrose consumption, increased FST and TST immobility time. While BA (25, 50 mg/kg) significantly attenuated these changes. Besides, BA treatment considerably inhibited inflammatory cytokinesl (IL-1β, IL-6, TNF-α) levels in serum, hippocampus homogenate and cell culture medium. Western blot analysis indicated that BA inhibited the expressions of HMGB1, TLR4, and p-NF-κBp65 both in vivo and in vitro. In conclusion, the present study confirmed that BA possessed efficient antidepressant effects on depression, which was possibly related to the inhibition of HMGB1/TLR4/NF-κB pathways.

Role of Interleukin-6 in Depressive Disorder

“…Baicalin, one of the main active ingredients of the traditional Chinese medicine drug Scutellaria radix, was investigated for its antidepressive effects in mice with chronic unpredictable mild stress [112]. Baicalin treatment showed antidepressant effects and considerably inhibited proinflammatory cytokine levels, including IL-6.…”

P2X7 receptor mediates NLRP3 inflammasome activation in depression and diabetes

“…Baicalin can penetrate BBB, has strong biological activity, and has been widely used in the clinical treatment of infectious and inflammatory disorders [82]. Preclinical studies have shown that baicalin exhibits antidepressant effects by inhibiting the GSK3β/ NF-κB/NLRP3 signaling pathway and downregulating overactivated HPA axis [83][84][85][86][87]. Moreover, baicalin can mitigate obesity and insulin resistance during diabetes treatment by activating the AKT/AS160/GLUT4 pathway and increasing the insulin sensitivity of lipocytes [88,89].…”

Potential Antidepressant Effects of Scutellaria baicalensis, Hericium erinaceus and Rhodiola rosea

“…In mice models of chronic (unrestraint) mild stress (CUMS), baicalin (25, 50 and 60 mg/kg) alleviates depression-like behavior by increasing sucrose consumption and reducing immobility times in the tail suspension and forced swim tests [138][139][140]. These effects are associated with a reduction of inflammatory cytokines IL-1β, IL-6, and TNF-α levels in serum and in the hippocampus [138,139]. In mice subjected to CUMS baicalin also abrogates the increase in NMDAR/NR2B and Ca2+/calmodulin-dependent protein kinase II (CaMPK-II) as well as the decrease in pERK, while counteracting reactive oxygen species (ROS) production [138].…”

“…In mice subjected to CUMS baicalin also abrogates the increase in NMDAR/NR2B and Ca2+/calmodulin-dependent protein kinase II (CaMPK-II) as well as the decrease in pERK, while counteracting reactive oxygen species (ROS) production [138]. Baicalin administration also counteracts CUMS-and neuroinflammation (LPS)-induced depressive-like behavior in mice, and this occurs through downregulation of TLR4 via the HMBG1/NF-kb [139] and PI3K/AKT/FoxO1 pathways [140].…”

“…Saliroside (20 and 40 mg/kg) [19,20] ↓TNF-α, IL-1β, IL-6 and NF-κB in the hippocampus and prefrontal cortex ↑BDNF expression in the hippocampus [19,20] ↑5-HT and NE levels in the prefrontal cortex [20] ↓CRF expression in hypothalamus and ↓serum corticosterone levels [19]. [144] ↓TLR4 via the HMBG1/NF-kb and PI3K/AKT/FoxO1 pathways [139,140]. ↑SOD and ↓ROS, MDA and caspase 1 [138,141] via ↓NMDAR/NR2B, ↓Ca2+/CaMPK-II and ↑pERK [139], and ↓GSK3β/ NF-κB / NLRP3 [141,142] ↓ultrastructural hippocampal alterations ↑synaptic proteins SYP PSD95, TrkB, Rac1, cofilin ↑BDNF [143] ↑neurogenesis (DCX-positive cells) ↑neuronal maturation, differentiation and survival [145].…”