Antidepressant effects of total iridoids of Valeriana jatamansi via the intestinal flora-blood–brain barrier pathway

Abstract

Context

Valeriana jatamansi Jones [syn. V. wallichii 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 Lactobacillus (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 × 10⁻³ or 14.60 ± 2.00 × 10⁻³ or 14.90 ± 2.00 × 10⁻³ vs.13.80 ± 4.00 × 10⁻³%), replication and repair functions (5.60 ± 1.00 × 10⁻³ or 5.60 ± 1.00 × 10⁻³ vs. 5.10 ± 4.00 × 10⁻³%), reduced the frequency of infectious disease (1.60 ± 2.00 × 10⁻⁴ or 1.90 ± 5.00 × 10⁻⁴ or 1.80 ± 3.00 × 10⁻⁴ vs. 2.20 ± 7.00 × 10⁻³%), 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.

Keywords:

• Depression
• blood–brain barrier (BBB) permeability
• firmicutes
• lactobacillus
• bacteroidetes
• functional prediction

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Correction

Disclosure statement

The authors declare that they have no conflict of interest.

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/10.1080/13880209.2023.2235925).

Additional information

Funding

This research was supported by the Fundamental Research Funds for the Central Universities [grant number 2682020ZT81], the Sichuan Province Academic and Technical Leaders Cultivate Support Funds, the Key Project of Research and Development Plan of Science and Technology Department of Sichuan Province [grant number 2018SZ0078, 2020JDZH0018], the Special Research Project of Sichuan Provincial Administration of Traditional Chinese medicine [grant number 2020JC0127, 2021MS099].