Rikkunshito improves anorexia through ghrelin- and orexin-dependent activation of the brain hypothalamus and mesolimbic dopaminergic pathway in rats.

Yakabi K, Yamaguchi N, Takayama K, Hosomi E, Hori Y, Ro S, Ochiai M, Maezawa K, Yakabi S, Harada Y, Fujitsuka N, Nagoshi S

Neurogastroenterology and motility20 Aug 2024Cited by 3 (Europe PMC)

PMID39164871DOI10.1111/nmo.14900PepBankPUB-39164871

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Summary

BackgroundRikkunshito (RKT), a traditional Japanese medicine, can relieve epigastric discomfort and anorexia in patients with functional dyspepsia. RKT enhances the orexigenic hormone, ghrelin. Ghrelin regulates food motivation by stimulating the appetite control center in the hypothalamus and the brain mesolimbic dopaminergic pathway (MDPW). However, the effect of RKT on MDPW remains unclear. Here, we aimed to investigate the central neural mechanisms underlying the orexigenic effects of RKT, focusing on the MDPW.MethodsWe examined the effects of RKT on food intake and neuronal c-Fos expression in restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats.Key resultsRKT treatment significantly restored stress- and cholecystokinin octapeptide-induced decreased food intake. RKT increased c-Fos expression in the ventral tegmental area (VTA), especially in tyrosine hydroxylase-immunoreactive neurons, and nucleus accumbens (NAc). The effects of RKT were suppressed by the ghrelin receptor antagonist [D-Lys³]-GHRP-6. RKT increased the number of c-Fos/orexin-double-positive neurons in the lateral hypothalamus (LH), which project to the VTA. The orexin receptor antagonist, SB334867, suppressed RKT-induced increase in food intake and c-Fos expression in the LH, VTA, and NAc. RKT increased c-Fos expression in the arcuate nucleus and nucleus of the solitary tract of the medulla, which was inhibited by [D-Lys³]-GHRP-6.Conclusions & inferencesRKT may restore appetite in subjects with anorexia through ghrelin- and orexin-dependent activation of neurons regulating the brain appetite control network, including the hypothalamus and MDPW.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone5

In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking GHRP-6.

01AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In male rats with induced anorexia, [D-Lys3]-GHRP‑6 suppressed RKT effects on food intake.
In plain wordsIn male rats with induced anorexia, [D-Lys3]-GHRP‑6 suppressed the food intake response compared with rikkunshito alone.
Peptide
GHRP-6
Outcome
DecreaseFood intake response to RKT
Study
ratn: not reported in source
Restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats
Comparator
Rikkunshito without antagonist
Outcome group
Appetite and food intake · Nervous system and cognition
Source sentences
Summary
The effects of RKT were suppressed by the ghrelin receptor antagonist [D-Lys³]-GHRP-6.
2 context sentences(design, population, supporting numbers)
Summary · context
RKT treatment significantly restored stress- and cholecystokinin octapeptide-induced decreased food intake.
Summary · context
We examined the effects of RKT on food intake and neuronal c-Fos expression in restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3916487101
02AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In male rats, [D-Lys3]-GHRP‑6 suppressed RKT-induced c-Fos expression in the VTA.
In plain wordsIn male rats, [D-Lys3]-GHRP‑6 suppressed the rikkunshito-induced c-Fos increase in the VTA compared with rikkunshito alone.
Peptide
GHRP-6
Outcome
DecreaseVTA c-Fos response to RKT
Study
ratn: not reported in source
Restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats
Comparator
Rikkunshito without antagonist
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
The effects of RKT were suppressed by the ghrelin receptor antagonist [D-Lys³]-GHRP-6.
2 context sentences(design, population, supporting numbers)
Summary · context
RKT increased c-Fos expression in the ventral tegmental area (VTA), especially in tyrosine hydroxylase-immunoreactive neurons, and nucleus accumbens (NAc).
Summary · context
We examined the effects of RKT on food intake and neuronal c-Fos expression in restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3916487102
03AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In male rats, [D-Lys3]-GHRP‑6 suppressed RKT-induced c-Fos expression in the NAc.
In plain wordsIn male rats, [D-Lys3]-GHRP‑6 suppressed the rikkunshito-induced c-Fos increase in the NAc compared with rikkunshito alone.
Peptide
GHRP-6
Outcome
DecreaseNAc c-Fos response to RKT
Study
ratn: not reported in source
Restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats
Comparator
Rikkunshito without antagonist
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
The effects of RKT were suppressed by the ghrelin receptor antagonist [D-Lys³]-GHRP-6.
2 context sentences(design, population, supporting numbers)
Summary · context
RKT increased c-Fos expression in the ventral tegmental area (VTA), especially in tyrosine hydroxylase-immunoreactive neurons, and nucleus accumbens (NAc).
Summary · context
We examined the effects of RKT on food intake and neuronal c-Fos expression in restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3916487103
04AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In male rats, [D-Lys3]-GHRP‑6 inhibited the RKT-induced c-Fos increase in the arcuate nucleus.
In plain wordsIn male rats, [D-Lys3]-GHRP‑6 suppressed the rikkunshito-induced c-Fos increase in the arcuate nucleus compared with rikkunshito alone.
Peptide
GHRP-6
Outcome
DecreaseArcuate nucleus c-Fos response to RKT
Study
ratn: not reported in source
Restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats
Comparator
Rikkunshito without antagonist
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
RKT increased c-Fos expression in the arcuate nucleus and nucleus of the solitary tract of the medulla, which was inhibited by [D-Lys³]-GHRP-6.
1 context sentence(design, population, supporting numbers)
Summary · context
We examined the effects of RKT on food intake and neuronal c-Fos expression in restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3916487104
05AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In male rats, [D-Lys3]-GHRP‑6 inhibited the RKT-induced c-Fos increase in the nucleus of the solitary tract.
In plain wordsIn male rats, [D-Lys3]-GHRP‑6 suppressed the rikkunshito-induced c-Fos increase in the nucleus of the solitary tract compared with rikkunshito alone.
Peptide
GHRP-6
Outcome
DecreaseSolitary tract nucleus c-Fos response to RKT
Study
ratn: not reported in source
Restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats
Comparator
Rikkunshito without antagonist
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
RKT increased c-Fos expression in the arcuate nucleus and nucleus of the solitary tract of the medulla, which was inhibited by [D-Lys³]-GHRP-6.
1 context sentence(design, population, supporting numbers)
Summary · context
We examined the effects of RKT on food intake and neuronal c-Fos expression in restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3916487105

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:13 UTC
First added · source update from Europe PMC

Subjects

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