7,8-Dihydroxyflavone Enhanced Colonic Cholinergic Contraction and Relieved Loperamide-Induced Constipation in Rats

Ma, Li; Qu, Zhe; Luo, Xu; Han, Lei; Han, Qingfang; He, Juan; Luan, Xiying; Wang, Bingxiang; Sun, Yongye; He, Baoguo

doi:10.1007/s10620-020-06817-y

Cited by 12 publications

(9 citation statements)

References 30 publications

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Section: Discussionsupporting

confidence: 92%

“…After 7 days of modeling, the stool samples of OIC rats became smaller and harder, while GI transit ratio and stool weight of these OIC rats significantly decreased. This was consistent with the characteristics of OIC stools in previous reports, indicating that the OIC rat model was successfully established (28,29). The functional activity of the GI tract is primarily regulated by the enteric nervous system (ENS), which mainly includes the submucosal plexus between the mucosa and the submucosa and the myenteric plexus located between the circular and longitudinal muscle (14,(41)(42)(43)(44).…”

Section: Discussionsupporting

confidence: 89%

“…SD rats were randomly divided into OIC (n=10), normal saline group (NSG; n=10), and normal control group (NCG; n=10). For the OIC group, rats were given i.p injection of loperamide hydrochloride dissolved in 0.9% normal saline (4 mg/kg; 1 ml/100 g) as previously described (26)(27)(28)(29) twice/day for 7 days. For NSG, 0.9% of normal saline (1 ml/100 g) was i.p injected twice/day for 7 days; rats in the NCG did not receive any treatment.…”

Section: Methodsmentioning

confidence: 99%

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P2Y1 receptor in the colonic submucosa of rats and its association with opioid‑induced constipation

Zhao

Ren

et al. 2022

Exp Ther Med

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The aim of the present study was to explore the expression changes of P2Y purinergic receptor 1 (P2Y1) in the distal colonic submucosa of opioid-induced constipation (OIC) rats and its association with the occurrence of OIC, an OIC rat model was generated by intraperitoneal injection of loperamide hydrochloride, a selective agonist of µ-opioid receptors (MORs). At 7 days post-treatment, the model was assessed by analyzing stool scores and calculating the gastrointestinal (GI) transit ratio of rats. The distribution of P2Y1-expressing neurons in the colonic submucosal plexus was demonstrated by immunofluorescence (IF). Western blotting was performed to evaluate the expression changes of MOR, P2Y1 and ATP synthase subunit β (ATPB) proteins in the colonic submucosa, while reverse transcription-quantitative PCR (RT-qPCR) analysis was performed to determine the relative mRNA expression of MOR and P2Y1. After 7 days, the feces of OIC rats exhibited an appearance of sausage-shaped pieces and both the stool weight and GI transit ratio of OIC rats were significantly decreased. IF revealed co-expression of P2Y1 and calbindin and MOR and ATPB in the nerve cells of the distal colonic submucosal plexus. Moreover, RT-qPCR analysis showed that the MOR mRNA levels were significantly increased in the distal colonic submucosa of OIC rats, while mRNA levels of P2Y1 were decreased. WB showed that in the distal colonic submucosa of OIC rats, MOR protein expression was increased, whereas that of P2Y1 was significantly decreased. GI transit ratio analysis suggested that the P2Y agonist ATP significantly relieved constipation symptoms in rats, while the P2Y inhibitor MRS2179 aggravated these symptoms. Finally, P2Y1 expression change was shown to be associated with the occurrence of OIC, while expression of MOR and P2Y1 was associated with OIC development in rats.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

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P2Y1 receptor in the colonic submucosa of rats and its association with opioid‑induced constipation

Zhao

Ren

et al. 2022

Exp Ther Med

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“…Loperamide is a widely used antidiarrhea drug in clinic, which inhibits the release of acetylcholine and prostaglandin and inhibits intestinal mucus secretion [ 30 ]. An STC rat model can be induced by intragastric administration of loperamide [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Improves Intestinal Motility through Exosomal miR-34c-5p Targeting SCF/c-Kit Signaling Pathway in Slow Transit Constipation Model Rats

Kuang

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. The pathogenesis of slow transit constipation (STC) is associated with exosomal miR-34c-5p. Electroacupuncture (EA) improves gastrointestinal motility in gastrointestinal disorders, especially STC. Our study aimed to explore the mechanism by which EA improves intestinal motility by modulating the release of exosomes and the transmission of exosomal miR-34c-5p. Methods. Fifty rats were randomly divided into five groups. STC model rats were induced, and GW4869, the exosome release inhibitor, was used to inhibit the release of exosome. The serum exosomes were authenticated under a transmission electron microscope and nanoparticle tracking analysis. RT-qPCR detected the expression of miR-34c-5p in serum exosomes and colonic tissues. The fecal number in 24 hours, Bristol scores, and intestinal transit rates were used to assess intestinal motility. Subsequently, hematoxylin and eosin (H&E) staining was used to examine the colonic mucosal histology. Finally, the expression of stem cell factor (SCF) and receptor tyrosine kinase (c-Kit) protein was measured using immunohistochemistry staining. Results. We found that EA upregulated exosomal miR-34c-5p in serum and downregulated miR-34c-5p in colonic tissues ( P < 0.01 ). EA improved fecal numbers in 24 hours, Bristol scores, and intestinal transit rates in STC rats ( P < 0.01 ). EA recovered the colonic histological structure and enhanced the expression of SCF and c-Kit protein ( P < 0.01 ). The therapeutic effect of EA was attenuated after inhibiting the release of the exosome. Conclusion. Our results indicated that EA improves intestinal motility in STC rats by transporting of exosomal miR-34c-5p targeting the SCF/c-Kit signaling pathway.

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“…In 2010, Jang et al reported that 7,8-DHF could penetrate the blood-brain barrier (BBB), simulate the BDNF effect, and selectively activate TrkB receptors, which has a strong protective effect on neurons [ 19 ]. Since then, 7,8-DHF has attracted wide attention as a high-affinity TrkB small molecule agonist and has been extensively investigated in diseases related to the BDNF-TrkB signaling pathway, including schizophrenia [ 20 ], anxiety disorders [ 21 ], gastrointestinal diseases [ 22 ], metabolic syndrome [ 23 ], cardiovascular diseases [ 24 ], Huntington’s disease (HD) [ 25 , 26 ], and Down syndrome (DS) [ 27 - 29 ] (Fig. 2 ).…”

Section: Introductionmentioning

confidence: 99%

7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational Perspective from the Mechanism to Drug Development

Yang

Zhu

2022

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: 7,8-Dihydroxyflavone (7,8-DHF) is a kind of natural flavonoids, with the potential to cross the blood-brain barrier. 7,8-DHF effectively mimics the effect of brain-derived neurotrophic factor (BDNF) in the brain to selectively activate tyrosine kinase receptor B (TrkB) and downstream signaling pathways, thus playing a neuroprotective role. The preclinical effects of 7,8-DHF have been widely investigated in the neuropsychiatric disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), depression and memory impairment. Besides the effect on TrkB, 7,8-DHF could also function through fighting against oxidative stress, cooperating with estrogen receptors or regulating intestinal flora. This review focuses on the recent experimental studies on depression, neurodegenerative diseases and learning and memory function. Additionally, the structural modification and preparation of 7,8-DHF were also concluded and proposed, hoping to provide reference for the follow-up research and clinical drug development of 7,8-DHF in the field of neuropsychiatric disorders.

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7,8-Dihydroxyflavone Enhanced Colonic Cholinergic Contraction and Relieved Loperamide-Induced Constipation in Rats

Cited by 12 publications

References 30 publications

P2Y1 receptor in the colonic submucosa of rats and its association with opioid‑induced constipation

P2Y1 receptor in the colonic submucosa of rats and its association with opioid‑induced constipation

Electroacupuncture Improves Intestinal Motility through Exosomal miR-34c-5p Targeting SCF/c-Kit Signaling Pathway in Slow Transit Constipation Model Rats

7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational Perspective from the Mechanism to Drug Development

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