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Complement C3-Deficiency-Induced Constipation in FVB/N-C3^em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts.

ABSTRACT: Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3^em1Hlee/Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The stool parameters and gastrointestinal (GI) transit were increased in Urd- and AEtLP-treated C3 KO mice compared with the vehicle (Veh)-treated C3 KO mice. Urd and AEtLP treatment improved the histological structure, junctional complexes of the intestinal epithelial barrier (IEB), mucin secretion ability, and water retention capacity. Also, an improvement in the composition of neuronal cells, the regulation of excitatory function mediated via the 5-hydroxytryptamine (5-HT) receptors and muscarinic acetylcholine receptors (mAChRs), and the regulation of the inhibitory function mediated via the neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) were detected in the enteric nervous system (ENS) of Urd- and AEtLP-treated C3 KO mice. Therefore, the results of the present study suggest that C3-deficiency-induced constipation can improve with treatment with Urd and AEtLP via the regulation of the mucin secretion ability, water retention capacity, and ENS function.

SUBMITTER: Song HJ

PROVIDER: S-EPMC10649790 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts.

Song Hee-Jin HJ Kim Ji-Eun JE Jin You-Jeong YJ Roh Yu-Jeong YJ Seol Ayun A Kim Tae-Ryeol TR Park Ki-Ho KH Park Eun-Seo ES An Beum-Soo BS Yang Seung-Yun SY Seo Sungbaek S Jo Seong-Min SM Jung Young-Suk YS Hwang Dae-Youn DY

International journal of molecular sciences 20231030 21

Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3em1Hlee/Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The st ...[more]

PMID: 37958740

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Project description:Liriope platyphylla (Liliaceae), a medical plant distributed mainly in China, Taiwan, and Korea, has been used traditionally for the treatment of cough, sputum, asthma, and neurodegenerative diseases. The present study involved the metabolic profiling of this plant and reports spicatoside A accumulation in four different varieties of L. platyphylla (Cheongyangjaerae, Seongsoo, Cheongsim, and Liriope Tuber No. 1) using HPLC and gas chromatography time-of-flight mass spectrometry (GC⁻TOFMS). A total of 47 metabolites were detected in the different cultivars using GC⁻TOFMS-based metabolic profiling. The resulting data were subjected to principal component analysis (PCA) for determining the whole experimental variation, and the different cultivars were separated by score plots. Furthermore, hierarchical clustering, Pearson's correlation, and partial least-squares discriminant analyses (PLS-DA) were subsequently performed to determine significant differences in the various metabolites of the cultivars. The HPLC data revealed that the presence of spicatoside A was detected in all four cultivars, with the amount of spicatoside A varying among them. Among the cultivars, Liriope Tuber No. 1 contained the highest amount of spicatoside A (1.83 ± 0.13 mg/g dry weight), followed by Cheongyangjaerae (1.25 ± 0.01 mg/g dry weight), Cheongsim (1.09 ± 0.04 mg/g dry weight), and Seongsoo (1.01 ± 0.02 mg/g dry weight). The identification of spicatoside A was confirmed by comparing the retention time of the sample with the retention time of the standard. Moreover, the Cheongsim cultivar contained higher levels of phenolic compounds-including vanillic acid, quinic acid, gallic acid, chlorogenic acid, caffeic acid, and benzoic acid-than those of the other two cultivars. On the other hand, the levels of amino acids were higher in the Seongsoo cultivar. Therefore, this study may help breeders produce new varieties with improved nutraceutical and nutritional qualities.

Project description:The prevalence of seizures in individuals with fragile X syndrome (FXS) is ~25%; however, there are no reports of spontaneous seizures in the Fmr1 knockout mouse model of FXS. Herein, we report that 48% of adult (median age P96), Fmr1 knockout mice from our colony were found expired in their home cages. We observed and recorded adult Fmr1 knockout mice having spontaneous convulsions in their home cages. In addition, we captured by electroencephalography an adult Fmr1 knockout mouse having a spontaneous seizure-during preictal, ictal, and postictal phases-which confirmed the presence of a generalized seizure. We did not observe this phenotype in control conspecifics or in juvenile (age <P35) Fmr1 knockout mice. We hypothesized that chronic, random, noise perturbations during development caused the phenotype. We recorded decibels (dB) in our vivarium. The average was 61 dB, but operating the automatic door to the vivarium caused spikes to 95 dB. We modified the door to eliminate noise spikes, which reduced unexpected deaths to 33% in Fmr1 knockout mice raised from birth in this environment (P = 0.07). As the modifications did not eliminate unexpected deaths, we further hypothesized that building vibrations may also be a contributing factor. After installing anti-vibration pads underneath housing carts, unexpected deaths of Fmr1 knockout mice born and raised in this environment decreased to 29% (P < 0.01 compared to the original environment). We also observed significant sex effects, for example, after interventions to reduce sound and vibration, significantly fewer male, but not female, Fmr1 knockout mice died unexpectedly (P < 0.001). The spontaneous seizure phenotype in our Fmr1 knockout mice could serve as a model of seizures observed in individuals with FXS, potentially offering a new translationally-valid phenotype for FXS research. Finally, these observations, although anomalous, serve as a reminder to consider gene-environment interactions when interpreting data derived from Fmr1 knockout mice.

Dataset Information

Complement C3-Deficiency-Induced Constipation in FVB/N-C3^em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts.

Publications

Complement C3-Deficiency-Induced Constipation in FVB/N-C3<sup>em1Hlee</sup>/Korl Knockout Mice Was Significantly Relieved by Uridine and <i>Liriope platyphylla</i> L. Extracts.

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