Antidepressant effects of total iridoids of via the intestinal flora-blood-brain barrier pathway.

CONTEXT

Jones [syn. DC, (Valerianaceae)] (VJJ) is used to treat depression.

OBJECTIVE

To explore the effects of total iridoids of VJJ extract (TIV) on chronic unpredictable mild stress (CUMS) in mice.

MATERIALS AND METHODS

VJJ roots and rhizomes were extracted with 70% ethanol. CUMS rats were treated daily with fluoxetine (2.6 mg/kg, i.g.) or TIV (5.7, 11.4, and 22.8 mg/kg, i.g.) for 14 days. Male Kun Ming mice on normal chow and 0.5% CMC-Na solution were used as a control. Behavioural tests included the tail suspension (TST) and sucrose preference tests (SPT). Evans blue staining was used to evaluate blood-brain barrier (BBB) permeability. Western blotting was used to measure zonula occludens-1 (ZO-1) and occludin expression. 16S rRNA sequencing was used to analyse intestinal flora abundance. Tax4Fun was used to predict KEGG metabolic pathways.

RESULTS

TIV treatment reduced TST time (117.35 ± 8.23 or 108.95 ± 6.76 vs. 144.45 ± 10.30 s), increased SPT (55.83 ± 7.24 or 53.12 ± 13.85 vs. 38.98 ± 5.43%), increased the abundance of phylum Firmicutes (86.99 ± 0.03 vs. 60.88 ± 0.19%) and genus (75.20 ± 0.19 vs. 62.10 ± 0.13%), reduced the abundance of phylum Bacteroidetes (6.69 ± 0.06 or 11.50 ± 0.09 vs. 25.07 ± 0.20%). TIV increased carbohydrate metabolism (14.50 ± 3.00 × 10 or 14.60 ± 2.00 × 10 or 14.90 ± 2.00 × 10 vs.13.80 ± 4.00 × 10%), replication and repair functions (5.60 ± 1.00 × 10 or 5.60 ± 1.00 × 10 vs. 5.10 ± 4.00 × 10%), reduced the frequency of infectious disease (1.60 ± 2.00 × 10 or 1.90 ± 5.00 × 10 or 1.80 ± 3.00 × 10 vs. 2.20 ± 7.00 × 10%), BBB permeability (0.77 ± 0.30 vs. 1.81 ± 0.33 μg/g), and up-regulated the expression of ZO-1 (1.42-fold, 1.60-fold, 1.71-fold) and occludin (1.79-fold, 2.20-fold).

CONCLUSIONS

TIV may modulate the intestinal flora, thereby inducing the expression of ZO-1 and occludin, protecting the BBB and exerting an antidepressant effect.