Antidepressant Effects and Mechanisms of the Total Iridoids of Valeriana jatamansi on the Brain-Gut Axis

Wang, Liwen; Sun, Yong; Zhao, Tingting; Li, Yongbiao; Zhao, Xing‐Ming; Zhang, Li; Wu, Lei; Zhang, Liudai; Zhang, Tiane; Wei, Guihua; Altamirano, Alvin; Yan, Tao; Zhang, Yan

doi:10.1055/a-1068-9686

Cited by 21 publications

(13 citation statements)

References 35 publications

(33 reference statements)

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“…The lethal dose with 50% mortality rate (LD 50 ) on mice is over 2000 mg/kg bw (Xu et al 2015). We also showed that TIV exerts an antidepressive effect by regulating multiple metabolic pathways (Li et al 2020) and regulates the intestinal flora in depressed mice (Wang et al 2020). What remains unclear is how the intestinal flora and BBB are involved in the anti-depression activities of TIV.…”

Section: Introductionmentioning

confidence: 93%

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

Zhang

Wang

Huang

et al. 2021

Pharmaceutical Biology

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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.

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Section: Introductionmentioning

confidence: 93%

“… 2020 ) and regulates the intestinal flora in depressed mice (Wang et al. 2020 ). What remains unclear is how the intestinal flora and BBB are involved in the anti-depression activities of TIV.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Wang

Huang

et al. 2021

Pharmaceutical Biology

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“…Bacterial commensals in the gut communicate with the CNS via metabolites and immune mediators, which regulates brain neurochemistry and behavior (Wang et al, 2019). SCFAs are the main metabolites of the intestinal flora, could provide energy directly to nerve cells through the BBB and act as signaling molecules.…”

Section: Discussionmentioning

confidence: 99%

“…in LPS-induced mice, contributing to the release of pro-inflammatory cytokines and brain inflammation eventually. As expected, SCE and SCL treatment significantly attenuated LPS-induced inflammation both in the CNS and periphery, and modulated neuroinflammation by repressing TLR4/NF-κB/IKKα signaling pathway.Bacterial commensals in the gut communicate with the CNS via metabolites and immune mediators, which regulates brain neurochemistry and behavior(Wang et al, 2019). SCFAs are the main F I G U R E 2 Effects of fractions treatment on LPSinduced histopathological changes in colon (H&E staining, 100 μm) [Colour figure can be viewed at wileyonlinelibrary.com] U R E 3 RT-PCR analysis of fractions on TLR4/NF-κB/IKKα signaling pathway in hippocampus of LPS-induced mice.…”

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confidence: 99%

Schisandra chinensis ameliorates depressive‐like behaviors by regulating microbiota‐gut‐brain axis via its anti‐inflammation activity

Yan

Wang

Liu

et al. 2020

Phytotherapy Research

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The present study aimed to examine the antidepressant actions of the composition fractions of Schisandra chinensis using LPS‐induced mice. Animals were treated with total extracts (SCE), lignans (SCL), polysaccharides (SCPS), and essential oil (SCVO), and then subjected to behavioral tests. The forced swimming test (FST) and tail suspension test (TST) were used as predictive animal models of antidepressant activity. Total extracts and lignans significantly decreased the duration of immobility in FST and TST. We found that treatment with SCE and SCL could significantly decrease the levels of pro‐inflammatory cytokines both in the periphery and central nervous system (CNS). This was confirmed by the histopathological examination of the colon. The RT‐PCR results demonstrated that SCE and SCL could greatly inhibit the TLR4/NF‐κB/IKKα signaling pathway. In addition, the concentrations of Butyric acid and Propionic acid were upregulated by the administration, and the decreased diversity of intestinal microbiota and alterations of the relative proportions of Bacteroidetes and Firmicutes phylum members, Barnesiella and Lactobacillus genus members in LPS‐induced mice were restored as well. All results suggested that lignans is the effective fraction of S.chinensis to ameliorating depressive disorders, which its anti‐inflammation activity possibly involved in the bidirectional connection between gut microbiota and brain.

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“…Recently Li et al [ 47 ] demonstrated that the antidepressant activity of the iridoid-rich fraction from V. jatamansi in a chronic unpredictable mild stress mouse model is exerted by regulating several metabolic pathways such as the synthesis of neurotransmitters, the tricarboxylic acid cycle, and amino acid metabolism. Recent studies also using the same model indicated that that gut flora structures and regulation of serotonin, norepinephrine, substance P, and corticotropin-releasing factor in the brain and intestine, can be implicated in the antidepressant properties of this plant [ 94 ]. The enhancement of noradrenergic and/or dopaminergic transmission induced by valepotriates from this species in the mouse brain can be related to the facilitation of GABA [ 59 ].…”

Section: Molecular Mechanism Of Action Of Pharmacological Potentialmentioning

confidence: 99%

Plant Species of Sub-Family Valerianaceae—A Review on Its Effect on the Central Nervous System

Das

Shin

Tundis

et al. 2021

Plants

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Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispasmodic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valerianaofficinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed, Scopus, Sci Finder, Web of Science, Science Direct, NCBI, and Google Scholar. The search terms used for this review included Valerianaceae, Valeriana, Centranthus, Fedia, Patrinia, Nardostachys, Plectritis, and Valerianella, phytochemical composition, in vivo studies, Central Nervous System, neuroprotective, antidepressant, antinociceptive, anxiolytic, anxiety, preclinical and clinical studies.

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Antidepressant Effects and Mechanisms of the Total Iridoids of Valeriana jatamansi on the Brain-Gut Axis

Cited by 21 publications

References 35 publications

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

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

Schisandra chinensis ameliorates depressive‐like behaviors by regulating microbiota‐gut‐brain axis via its anti‐inflammation activity

Plant Species of Sub-Family Valerianaceae—A Review on Its Effect on the Central Nervous System

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