🧬 BDNF Extraction Viewer

Chaihu Shugan San (CSS), a classical Traditional Chinese Medicine (TCM) formula, was first recorded in Jingyue Quanshu (1624 AD) for treating "liver qi stagnation" (Yu Syndrome), a TCM diagnostic pattern analogous to modern mood disorders. Although CSS has been prescribed for emotional distress, irritability, and depressive symptoms for centuries, the neurobiological mechanisms underlying its antidepressant efficacy, particularly in the context of gender-specific pathology, remain poorly revealed. The present study probed the antidepressant effects of CSS in female mice, while elucidating the underlying molecular mechanisms involving hippocampal neuroinflammation and neuroplasticity. We hypothesized that CSS reverses chronic stress-induced depressive phenotypes by suppressing interleukin-6 (IL-6), which in turn facilitates cAMP-CaMKII-BDNF signaling pathway in the hippocampus. Adult female C57BL/6J mice were subjected to a 5-week chronic unpredictable mild stress (CUMS) regimen to evoke depressive-like behaviors. During the final 2 weeks of the regimen, CSS was administered intragastrically at 0.5, 1.0, or 1.5 g/kg, with fluoxetine (10 mg/kg) as the positive control. Behavioral assessments included forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), and tail suspension test (TST). Hippocampal IL-6, cAMP, CaMKII, and BDNF levels were quantified by ELISA. Mechanistic validation employed acute hippocampal microinjection of recombinant IL-6 (1 μg/site) and systemic administration of the CaMKII inhibitor KN-93 (6 mg/kg). Chemical constituents were identified by UHPLC-QTOF MS. CSS alleviated CUMS-induced depressive-like behaviors in a dose-dependent manner, cutting down immobility time in TST/FST and reinstating sucrose preference, similar to the action of fluoxetine. CSS significantly suppressed hippocampal IL-6 while upregulating cAMP, CaMKII activity, and BDNF expression. Acute IL-6 elevation completely abolished both the behavioral antidepressant effects and molecular actions of CSS. Pharmacological inhibition of CaMKII blocked CSS-induced behavioral improvement and its upregulation of cAMP-BDNF signaling, without affecting basal behaviors. CSS exhibited no anxiogenic or locomotor side effects. CSS exerts potent antidepressant effects in female mice through coordinated suppression of hippocampal IL-6 and activation of the cAMP-CaMKII-BDNF neuroplasticity-related pathway, with CaMKII playing a critical role in this process. These findings offer scientific evidence for the traditional use of CSS in addressing emotional disorders and highlight its therapeutic potential as a multi-targeted, anti-inflammatory botanical medicine for female-specific depression.