NaHS inhibits NF-κB signal against inflammation and oxidative stress in post-infectious irritable bowel syndrome

Yang, Shan; Deng, Danfang; Luo, Yingying; Wu, Yanran; Zhu, Rui; Xue, Ke; Zhou, Yanping

doi:10.1039/c6ra13849g

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…Oxidative stress and inflammation play pivotal roles in the occurrence and persistence of PI-IBS symptoms ( Yang et al, 2016 ). In the current study, the levels of oxidative stress and inflammation markers were detected by ELISA in serum and colon tissue lysates of Trichinella spiralis -infected mice as well as in NCM460 cells treated with LPS in the presence or absence of ALW-II-41-27.…”

Section: Resultsmentioning

confidence: 99%

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A Novel EphA2 Inhibitor Exerts Beneficial Effects in PI-IBS in Vivo and in Vitro Models via Nrf2 and NF-κB Signaling Pathways

Zeng

Hong

et al. 2018

Front. Pharmacol.

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Though the detailed pathological mechanism of post-infectious irritable bowel syndrome (PI-IBS) remains unclear, accumulating evidence indicates that oxidative stress and inflammation are implicated in the process of PI-IBS. Oxidative stress and inflammation are regulated by Nrf2 and NF-κB signaling pathways, respectively. EphA2, a member of Eph receptor family, promotes oxidative stress and inflammatory responses via regulation of Nrf2 and NF-κB signaling pathways in various types of human diseases. Understanding the mechanisms by which EphA2 regulate oxidative stress and inflammation in PI-IBS is important for the development of new strategies to treat PI-IBS. However, the effects of ALW-II-41-27, a novel EphA2 inhibitor on PI-IBS and the underlying molecular mechanisms have never been studied. In the present study, we showed that ALW-II-41-27 decreased gastrointestinal motility and abdominal withdrawal reflex (AWR) scores, markedly reduced the levels of oxidative stress markers [4-hydroxy-2-nonenal (4-HNE), protein carbonyl, and 8-hydroxy-2-de-axyguanine (8-OHdG)] and proinflammatory cytokines (TNF-α, IL-6, IL-17, and ICAM-1), and remarkably increased the level of anti-inflammatory cytokine (IL-10) in serum and colon of Trichinella spiralis-infected mice. Moreover, ALW-II-41-27 was effective in suppressing oxidative stress and inflammation in LPS-treated NCM460 colonic cells. Treatment of ALW-II-41-27 reversed the activation of NF-κB and inactivation of Nrf2 in LPS-treated NCM460 cells. Importantly, these protective effects of ALW-II-41-27 were partially inhibited by EphA2 KO and abolished by EphA2 overexpression. In conclusion, EphA2 may represent a promising therapeutic target for patients with PI-IBS and ALW-II-41-27 might function as a novel therapeutic agent for PI-IBS.

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Section: Resultsmentioning

confidence: 99%

“…Oxidative stress and inflammation are regulated by Nrf2 and NF-κB signaling pathways, respectively. NF-κB signaling is well-known for its roles in regulation of inflammation ( Yang et al, 2016 ). HO-1 is a critical phase II antioxidant enzyme that participates in suppression of oxidative stress ( Rizzardini et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

A Novel EphA2 Inhibitor Exerts Beneficial Effects in PI-IBS in Vivo and in Vitro Models via Nrf2 and NF-κB Signaling Pathways

Zeng

Hong

et al. 2018

Front. Pharmacol.

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“…TNF-α is known to induce inflammation in intestinal epithelial cells [ 17 , 18 , 19 ]. Consistently, a 24 h TNF-α treatment at 5 ng/mL resulted in inflammation in Caco-2 cells as shown by enhanced phosphorylation of p65 and reduced total p65 protein content ( Figure 5 ).…”

Section: Resultsmentioning

confidence: 99%

Effect of Cooking Methods on Bioactivity of Polyphenols in Purple Potatoes

Sun

Navarre

et al. 2021

Antioxidants

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Purple-fleshed potato (Solanum tuberosum L.) is a good dietary source of anthocyanins, flavonols, and polyphenolic acids, mostly chlorogenic acid. The objective of this study was to examine the impacts of cooking methods including boiling, steaming, and the newly developed vacuum-sealed boiling (VSBoil) on extractability and bioactivity of polyphenolic compounds in a purple potato (PP) cultivar, Purple Pelisse. Data showed that boiling and steaming reduced the total polyphenolic content in PP. High-performance liquid chromatography analysis showed that steaming slightly reduced the extractable chlorogenic acid content, while VSBoil increased it. For DPPH free radical scavenging activities, VSBoil and steaming effectively preserved the antioxidant activity of a polyphenol-rich extract of PP, while boiling resulted in a significant reduction compared to raw potato extract. All extracts effectively suppressed bursts of intracellular reactive oxygen species in human colonic epithelial cells upon hydrogen peroxide induction, of which the extract from the VSBoil group showed the highest antioxidant potential. In addition, all extracts showed anti-inflammatory effects in Caco-2 cells induced with tumor necrosis factor-α. In conclusion, the content and bioactivity of extractable polyphenols were largely retained in PP subjected to different cooking processes. VSBoil resulted in the highest content of extractable polyphenolic compounds and bioactivity among tested cooking methods.

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“…Sodium hydrogen sulfide (NaHS), an H 2 S donor, injection was demonstrated to markedly alleviate inflammation and oxidative stress in post-infectious IBS. 21 Moreover, the upregulated CBS/H 2 S signaling in the dorsal root ganglion neurons innervating the colon was suggested to contribute to chronic visceral hyperalgesia in a rat model of IBS. 22 To date, H 2 S is emerging as a modulator of gastrointestinal motility in multiple diseases, but its involvement in IBS is still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, increasing researches have reported an important role of H 2 S in the pathophysiology of IBS. Sodium hydrogen sulfide (NaHS), an H 2 S donor, injection was demonstrated to markedly alleviate inflammation and oxidative stress in post‐infectious IBS 21 . Moreover, the upregulated CBS/H 2 S signaling in the dorsal root ganglion neurons innervating the colon was suggested to contribute to chronic visceral hyperalgesia in a rat model of IBS 22 .…”

Section: Discussionmentioning

confidence: 99%

Dysregulated cystathionine‐β‐synthase/hydrogen sulfide signaling promotes chronic stress‐induced colonic hypermotility in rats

Lin

2022

Neurogastroenterology Motil

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Background: Hydrogen sulfide (H 2 S), an important endogenous gasotransmitter, is involved in the modulation of gastrointestinal motility, but whether it mediates the intestinal dysmotility in irritable bowel syndrome (IBS) is not known. This study explored the significance of cystathionineβ-synthase (CBS)/H 2 S signaling in stressinduced colonic dysmotility.Methods: A rat model of IBS was established using chronic water avoidance stress (WAS). Colonic pathological alterations were detected histologically. Intestinal motility was determined by intestinal transit time (ITT) and fecal water content (FWC).Visceral sensitivity was assessed using the visceromotor response (VMR) to colorectal distension (CRD). Real-time PCR, Western blotting, and immunostaining were performed to identify the expression of CBS in the colon. The contractions of distal colon were studied in an organ bath system and H 2 S content was measured by ELISA.The effects of SAM, a selective CBS activator, on colonic dysmotility were examined.MEK1 was tested as a potential upstream effector of CBS/H 2 S loss.Key Results: After 10 days of WAS, the ITT was decreased and FWC was increased, and the VMR magnitude in response to CRD was enhanced. The colonic CBS expression and H 2 S levels were significantly declined in WAS-exposed rats, and the density of CBS-positive enteric neurons in the myenteric plexus in WAS-treated rats was lower than that in controls. SAM treatment relieved WAS-induced colonic hypermotility via increased H 2 S production. AZD6244, a selective inhibitor of MEK1, partially reversed CBS downregulation and colonic hypermotility in WAS-treated rats.Conclusions & Inferences: Decreased CBS/H 2 S signaling through increased MEK1 signaling might be important in the pathogenesis of chronic stress-induced colonic hypermotility. SAM could be administered for disorders associated with intestinal hypermotility.

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NaHS inhibits NF-κB signal against inflammation and oxidative stress in post-infectious irritable bowel syndrome

Cited by 6 publications

References 37 publications

A Novel EphA2 Inhibitor Exerts Beneficial Effects in PI-IBS in Vivo and in Vitro Models via Nrf2 and NF-κB Signaling Pathways

A Novel EphA2 Inhibitor Exerts Beneficial Effects in PI-IBS in Vivo and in Vitro Models via Nrf2 and NF-κB Signaling Pathways

Effect of Cooking Methods on Bioactivity of Polyphenols in Purple Potatoes

Dysregulated cystathionine‐β‐synthase/hydrogen sulfide signaling promotes chronic stress‐induced colonic hypermotility in rats

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