TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors

Layunta, Elena; Forcén, Raquel; Grasa, Laura

doi:10.3390/cells11111791

Cited by 4 publications

(3 citation statements)

References 51 publications

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“… 31 It is well established that after Ach activates CHRM3, CHRM3 coupling with Gq/G11 regulates intestinal smooth muscle contraction. 32 Both Ach as a neurotransmitter and CHRM3 as a member of GPCR have been confirmed to be activated in the IBS model in this experiment. Furthermore, following TXYF treatment, the expression of both Ach and CHRM3 was down-regulated.…”

Section: Discussionsupporting

confidence: 57%

Tongxieyaofang Decotion Alleviates IBS by Modulating CHRM3 and Gut Barrier

Feng,

Zhou,

et al. 2024

DDDT

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Purpose Through network pharmacology combined with molecular docking and in vivo validation, the study examines the unexplored molecular mechanisms of Tongxieyaofang (TXYF) in the treatment of irritable bowel syndrome (IBS). In particular, the potential pharmacological mechanism of TXYF alleviating IBS by regulating CHRM3 and intestinal barrier has not been studied. Patients and Methods LC-MS technique and TCMSP database were used in combination to identify the potential effective components and target sites of TXYF. Potential targets for IBS were obtained from Genecards and OMIM databases. PPI and cytoHub analysis for targets. Molecular docking was used to validate the binding energy of effective components with related targets and for visualization. GO and KEGG analysis were employed to identify target functions and signaling pathways. In the in vivo validation, wrap restraint stress-induced IBS model was employed to verify the change for cytoHub genes and CHRM3 expression. Furthermore, inflammatory changes of colon were observed by HE staining. The changes of Ach were verified by ELISA. IHC and WB validated CHRM3 and GNAQ/PLC/MLCK channel variations. AB-PAS test and WB test confirmed the protection of TXYF on gut barrier. The NF-κB/MLCK pathway was also verified. Results In TXYF decoction, LC-MS identified 559 chemical components, with 23 remaining effective components after screening in TCMSP. KEGG analysis indicated that calcium plays a crucial role in TXYF treated for IBS. Molecular docking validated the binding capacity of the effective components Naringenin and Nobiletin with cytoHub-gene and CHRM3. In vivo validation demonstrated that TXYF inhibits the activation of Ach and CHRM3 in IBS, and inhibits for the GNAQ/PLC/MLCK axis. Additionally, TXYF downregulates TNF-α, MMP9, and NF-κB/MLCK, while modulating goblet cell secretion to protect gut barrier. Conclusion TXYF inhibits Ach and CHRM3 expression, regulating the relaxation of intestinal smooth muscle via GNAQ/PLC/MLCK. Additionally, TXYF inhibits NF-κB/MLCK activated and goblet cell secretion to protect gut barrier.

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Section: Discussionsupporting

confidence: 57%

Tongxieyaofang Decotion Alleviates IBS by Modulating CHRM3 and Gut Barrier

Feng,

Zhou,

et al. 2024

DDDT

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“…A decreased expression of VIP is associated with impaired rectal sensory function and colonic motility ( 7 ). ACh released from parasympathetic nerves mediates muscle contraction ( 8 ). Moreover, interstitial cells of Cajal (ICC) are involved in regulating autonomic nerves that predominantly facilitate intestinal motility ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Luteolin ameliorates loperamide-induced functional constipation in mice

Wang

Jiang

Wang

et al. 2023

Braz J Med Biol Res

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Functional constipation (FC) is one of the most common gastrointestinal disorders characterized by hard stools and infrequent bowel movements, which is associated with dysfunction of the enteric nervous system and intestinal motility. Luteolin, a naturally occurring flavone, was reported to possess potential pharmacological activities on intestinal inflammation and nerve injury. This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoactive intestinal polypeptide (VIP), and acetylcholine (ACh), as well as interstitial cells of Cajal (ICC) biomarker KIT proto-oncogene, receptor tyrosine kinase (C-Kit), and anoctamin-1 (ANO1), implying that luteolin mediated enhancement of colonic function and contributed to the anti-intestinal dysmotility against loperamide-induced FC. Additionally, luteolin decreased the upregulation of aquaporin (AQP)-3, AQP-4, and AQP-8 in the colon of FC mice. In summary, our data showed that luteolin might be an attractive option for developing FC-relieving medications.

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“…In their study, Layunta et al evaluated the role of TLR2 and TLR4, both receptors involved in the recognition of intestinal bacteria, in the intestinal motor-response induced by acetylcholine (ACh) in the mouse ileum. The authors showed, for the first time, that TLR2 acts on muscarinic M2 and M3 and nicotinic α3β4 ACh receptors, whereas TLR4 acts on muscarinic M3 and nicotinic α3β4 and α7 ACh receptors [ 9 ].…”

mentioning

confidence: 99%