Daikenchuto, a traditional Japanese herbal medicine, promotes colonic transit by inducing a propulsive movement pattern.

BACKGROUND: The traditional Japanese herbal medicine, daikenchuto (DKT), has been used to treat constipation and postoperative ileus. However, the precise mechanisms involved in the pharmacological effects of DKT remain uncertain. The aim of this study was to clarify the effect of DKT on motor patterns and transit activity in the isolated rat colon. METHODS: The entire colon or segments of the proximal colon in rats were isolated and placed in Krebs solution. The motility of the colon was evaluated by analyzing spatiotemporal maps of diameter derived from video imaging and measuring the intraluminal pressure in the anal end of the proximal colon, and the transit time of a plastic bead through the entire isolated colon. KEY RESULTS: Several types of propagating contractions were observed in the isolated entire colon. When DKT was added to Krebs solution, the frequency of large-extent anal propagating contractions increased. DKT treatment increased the intraluminal pressure in the isolated proximal colon, which was related to the propagating contractions. This effect was abolished by treatment with the neural blocker tetrodotoxin. These findings suggest DKT induced peristaltic contractions in the isolated colon. DKT accelerated colonic transit activity, which was related to peristaltic contractions induction in the colon. These effects were also observed in the colons treated with bethanechol and the active ingredient of DKT, hydroxy-α-sanshool. CONCLUSIONS AND INFERENCES: Daikenchuto could enhance colonic transit activity by inducing peristaltic contractions, which may be mediated by the activation of the enteric nervous system in the colon.

Digestion of peptidoglycan near the cross-link is necessary for the growth of Bacillus subtilis.

Bacterial cells are covered with peptidoglycan (PG) layer(s), serving as the cellular exoskeleton. The PG sacculus changes its shape during cell growth, and thus both the synthesis and disassembly of PG are important for cell proliferation. In Bacillus subtilis, four dl-endopeptidases (DLEPases; LytE, LytF, CwlO and CwlS) are involved in the maintenance of cell morphology. The lytE cwlO double mutant exhibits synthetic lethality and defective cell elongation, while the lytE lytF cwlS triple mutant exhibits defective cell separation, albeit with septum formation. LytE is involved in both cell separation and elongation. We propose that DLEPases have varied roles in cell separation and elongation. To determine these roles, the catalytic domain of LytE was substituted with another catalytic domain that digests the other bonds in PG. By using the chimeric enzymes, we assessed the suppression of the synthetic lethality by the cell elongation defect and the disruption of chain morphology by the cell separation defect. All the constructed chimeric enzymes suppressed the cell separation defect, restoring the chain morphology. Digestion at any position of PG broke the linkage between two daughter cells, releasing them from each other. However, only d,d-endopeptidases suppressed the lack of DLEPase in the lytE cwlO double mutant. This indicated that the release of tension on the expanding PG sacculus is not the sole essential function of DLEPases. Considering that the structure of the digested PG is important for cell elongation, the digested product might be reused in the growth process in some way.

Oral administration of coenzyme Q10 reduces MPTP-induced loss of dopaminergic nerve terminals in the striatum in mice.

The neuroprotective effect of coenzyme Q(10) (CoQ(10)) has been reported in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. In this study, we investigated whether oral administration of CoQ(10) could protect the striatal dopaminergic (DAergic) nerve terminals against MPTP-induced toxicity in C57BL/6N mice using immunoisolation technique for DAergic synaptosomes. CoQ(10) significantly attenuated decrease in dopamine transporter as well as in synaptophysin and actin protein levels in DAergic synaptosomes from MPTP-treated mice. The effect of CoQ(10) was also observed in crude synaptosomes fraction, but not in homogenate. Our results indicate that the nerve terminals are a site for the action of CoQ(10) against the MPTP-induced DAergic neurodegeneration.

Oral administration of coenzyme Q(10) prevents cytochrome c release from mitochondria induced by 1-methyl-4-phenylpyridinium ion in mouse brain synaptosomes.

Coenzyme Q(10) (CoQ(10)) exerts neuroprotective effects in several in vivo and in vitro models of neurodegenerative disorders. However, the mechanisms of action are not fully understood. The aim in this study was to investigate whether oral administration of CoQ(10) could inhibit cytochrome c (cyt c) release from mitochondria induced by 1-methyl-4-phenylpyridinium ion (MPP(+)), which causes dopaminergic cell death by selective inhibition of complex I of the electron transport chain, in mouse brain synaptosomes. An increase of cyt c was detected in the cytosolic fraction from mouse brain synaptosomes treated with MPP(+). Oral administration of CoQ(10) prevented the mitochondrial cyt c release in the MPP(+)-treated synaptosomes. In addition, CoQ(10) did not affect the MPP(+)-induced decrease in mitochondrial oxidation-reduction activity and membrane potential in brain synaptosomes. Our findings demonstrate that MPP(+)-induced mitochondrial cyt c release in brain synaptosomes is prevented by oral administration of CoQ(10) independently of mitochondrial dysfunction prior to the cyt c release.

Enhanced susceptibility to MPTP neurotoxicity in magnesium-deficient C57BL/6N mice.

We evaluated the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6N mice fed a magnesium (Mg(2+))-deficient diet. On the 3rd week, Mg(2+)-deficient mice displayed increased anxiety- and depression-like behavior. In the Mg(2+)-deficient mice, a low does (10mg/kg) of MPTP treatment decreased dopamine (DA) and its metabolites contents in the striatum, but not in control mice. The same dose of MPTP did not influence these neurochemical markers in the mice fed Mg(2+)-deficient diet for 1 week which did not exhibit the altered emotional behavior. These results indicate that Mg(2+)-deficient mice with altered emotional behavior appear to increase the susceptibility to MPTP neurotoxicity in C57BL/6N mice.