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 Â 10 À3 or 14.60 ± 2.00 Â 10 À3 or 14.90 ± 2.00 Â 10 À3 vs.13.80 ± 4.00 Â 10 À3 %), replication and repair functions (5.60 ± 1.00 Â 10 À3 or 5.60 ± 1.00 Â 10 À3 vs. 5.10 ± 4.00 Â 10 À3 %), reduced the frequency of infectious disease (1.60 ± 2.00 Â 10 À4 or 1.90 ± 5.00 Â 10 À4 or 1.80 ± 3.00 Â 10 À4 vs. 2.20 ± 7.00 Â 10 À3 %), BBB permeability (0.77 ± 0.30 vs. 1.81 ± 0.33 lg/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.

Iridoids rich fraction from Valeriana jatamansi Jones promotes axonal regeneration and motor functional recovery after spinal cord injury through activation of the PI3K/Akt signaling pathway

“…For CNS, studies have corroborated that VJJ modulates the hypothalamic–pituitary–adrenal axis ( Yan et al, 2010 ; Shi et al, 2014 ), inhibit microglia activation ( Yang et al, 2022 ), and protect the blood–brain barrier ( Zhang B. et al, 2021 ; Zhang L. et al, 2021 ). Contrary to the findings of this study, VJJ has been previously demonstrated to inhibit rotavirus-induced diarrhoea by suppressing the PI3K/AKT signalling pathway ( Zhang et al, 2021 ), and 11-Ethoxyviburtinal, derived from VJJ, exerts anxiolytic effects through this pathway’s inhibition ( Lyu et al, 2023 ). These variations may stem from the distinct molecular mechanisms underlying various disorders and the diverse bioactive constituents present in VJJ.…”

“…Employed as an adjunctive therapy, TCM has shown to be advantageous in enhancing motor and sensory functions, as well as the daily living capabilities of individuals with SCI ( Zheng et al, 2020 ). VJJ, with its extensive historical application in TCM, exhibits a wide spectrum of biological activities, including sedative-hypnotic ( Sah et al, 2010 ), antianxiety and antidepressant ( Zhang B. et al, 2021 ; Zhang L. et al, 2021 ), anti-tumour properties ( Tian et al, 2020 ). For CNS, studies have corroborated that VJJ modulates the hypothalamic–pituitary–adrenal axis ( Yan et al, 2010 ; Shi et al, 2014 ), inhibit microglia activation ( Yang et al, 2022 ), and protect the blood–brain barrier ( Zhang B. et al, 2021 ; Zhang L. et al, 2021 ).…”

“…VJJ, with its extensive historical application in TCM, exhibits a wide spectrum of biological activities, including sedative-hypnotic ( Sah et al, 2010 ), antianxiety and antidepressant ( Zhang B. et al, 2021 ; Zhang L. et al, 2021 ), anti-tumour properties ( Tian et al, 2020 ). For CNS, studies have corroborated that VJJ modulates the hypothalamic–pituitary–adrenal axis ( Yan et al, 2010 ; Shi et al, 2014 ), inhibit microglia activation ( Yang et al, 2022 ), and protect the blood–brain barrier ( Zhang B. et al, 2021 ; Zhang L. et al, 2021 ). Contrary to the findings of this study, VJJ has been previously demonstrated to inhibit rotavirus-induced diarrhoea by suppressing the PI3K/AKT signalling pathway ( Zhang et al, 2021 ), and 11-Ethoxyviburtinal, derived from VJJ, exerts anxiolytic effects through this pathway’s inhibition ( Lyu et al, 2023 ).…”

Mechanism of Valeriana Jatamansi Jones for the treatment of spinal cord injury based on network pharmacology and molecular docking

“…infection, gastrointestinal bleeding, and pulmonary embolism, significantly increasing mortality. [4] Valeriana jatamansi Jones (VJJ), also known as Zhi zhu xiang, an oral Chinese herbal medicine with a long history of use, has a variety of biological functions, including sedativehypnotic, [5] antianxiety, antidepressant, [6] antibacterial, antiviral, [7] and antitumor [8] effects, without obvious signs of drug dependence or toxic effects. [9,10] VJJ is a Chinese herbal medicine with promising future development.…”

Therapeutic potential of plant iridoids in depression: a review

“…In addition, administration of TIV for 2 weeks in CUMS adult male KM mice could also elevate the expression of zonula occludens-1 (ZO-1) and occludin to reduce the BBB permeability and balance the relative abundance of firmicutes and bacteroidetes (Zhang L et al. 2021 ). According to a comprehensive serum metabolomics study using NMR, TIV may exert antidepressant effects through various metabolic pathways, including neurotransmitter synthesis, tricarboxylic acid cycle regulation, and amino acid metabolism (Li, Wu, et al.…”