Evidence map›Paper›PMID 40361157›Full record

ArticleBMC complementary medicine and therapies2025

Effects of Ninjin'yoeito and physical exercise on serum corticosterone and hippocampal BDNF/proBDNF and neuroinflammation in post-stroke depression in rats.

Harutoshi Sakakima, Nao Nojima, Akira Tani, Kazuki Nakanishi, Teruki Matsuoka, Ryoma Matsuzaki, Shogo Kakimoto, Yuki Kato, Yuta Tachibe, Masaki Inadome and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC complementary medicine and therapies, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Harutoshi Sakakima *Department of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan. sakaki@health.nop.kagoshima-u.ac.jp.
Nao Nojima *Department of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Akira Tani *Department of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Kazuki Nakanishi *Department of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Teruki MatsuokaDepartment of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Ryoma MatsuzakiDepartment of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Shogo KakimotoDepartment of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Yuki KatoDepartment of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Yuta TachibeDepartment of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Masaki InadomeDepartment of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Takuya KawataniDepartment of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Shotaro OtsukaFaculty of Welfare and Health Science, Oita University, Oita, Japan.
Keita MizunoKampo Research and Development Division, Tsumura Kampo Research Laboratories, Tsumura and Co., Ibaraki, Japan.
Ikuro MaruyamaDepartment of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Funding

Japan Society for the Promotion of Science JP20H04039
6 · The paper itself

Abstract

backgroundNinjin'yoeito (NYT), a traditional Japanese Kampo medicine, improves the depression and anxiety in humans and animals, rendering it a novel therapeutic option for post-stroke depression (PSD). Furthermore, physical exercise is an important nonpharmacological therapy for major depressive disorder. The components of NYT or exercise exert antidepressant effects through the increased expression of neurotrophic factors and reduced neuroinflammation in the brain. However, the mechanisms underlying the antidepressant effects of NYT and exercise in PSD remain unclear. Therefore, we examined the effects of NYT and physical exercise in a rat model of PSD.

methodsRats were divided into five groups: PSD, PSD with NYT, PSD with exercise (Ex), PSD with NYT and exercise (NYT + Ex), and control (sham). PSD was induced by the microinjection of endothelin-1 into the left medial prefrontal cortex and chronic unpredictable mild stress 3 days per week. A diet containing 3% NYT was administered to rats one day after stroke induction. Exercise was conducted using a motorized treadmill for three days per week, starting three days after the stroke. The therapeutic interventions lasted for four weeks. Serum corticosterone levels, depression-like behavior, and hippocampal pathophysiology, including the expression of brain-derived neurotrophic factor (BDNF), precursor BDNF (proBDNF), doublecortin (DCX), NeuN, glial cell activation, and tumor necrosis factor-α (TNF-α), were examined.

resultsSerum corticosterone levels were lower in the treatment group than those in the PSD group. Notably, serum corticosterone levels were significantly lower in the NYT group than those in the PSD group. BDNF expression in the CA1 region was significantly higher in the Ex group than that in the PSD group. The NYT + Ex group showed a significantly higher hippocampal BDNF/proBDNF ratio than the other groups. DCX and NeuN expression levels were significantly higher in the NYT + Ex group than those in the NYT and PSD groups. Hippocampal glial cell activation and TNF-α expression increased in the PSD group and decreased in the intervention groups.

conclusionsNYT ameliorates serum corticosterone levels and hippocampal neuroinflammation in PSD. Additionally, this study suggested that NYT, together with exercise therapy, may improve neurogenesis, the BDNF/proBDNF ratio, and neuroinflammation in the hippocampus in PSD. CLINICAL TRIAL NUMBER: Not applicable.

Indexed as

Brain-Derived Neurotrophic FactorCorticosteroneDepressionDrugs, Chinese HerbalNeuroinflammatory DiseasesPhysical Conditioning, AnimalStrokeAnimalsDisease Models, AnimalDoublecortin ProteinHippocampusMaleMedicine, KampoRatsRats, Sprague-DawleyBdnf protein, ratBrain-Derived Neurotrophic FactorCorticosteroneDcx protein, ratDoublecortin ProteinDrugs, Chinese HerbalNeurogenesisNeuroinflammationNeurotrophic factorNinjin’yoeitoPSDRehabilitation

Identifiers

PMID40361157
PMCPMC12070628

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.