Vildagliptin attenuates acetic acid-induced colitis in rats via targeting PI3K/Akt/NFκB, Nrf2 and CREB signaling pathways and the expression of lncRNA IFNG-AS1 and miR-146a

Fouad, Marina R.; Salama, Rania M.; Zaki, Hala F.; El-Sahar, Ayman E.

doi:10.1016/j.intimp.2020.107354

Cited by 24 publications

(13 citation statements)

References 57 publications

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“…Postmortem and clinical studies have shown that CREB and ERK levels in the cortex of patients with major depressive disorder are significantly lower than those of normal bodies (Wang & Mao, 2019). Decreased levels of CREB were found in multiple brain regions of CUMS model rats, and long‐term gavage of depressants could enhance the expression or phosphorylation of CREB, thereby further increasing BDNF expression (Fouad et al, 2021). In addition, BDNF can also bind to the downstream receptor TrkB to activate the ERK/CREB pathway to relieve depression, the ERK/CREB/BDNF pathway is considered to be an important cascade signal for the treatment of depression (Kandola et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Polygonum sibiricum polysaccharides exert the antidepressant‐like effects in chronic unpredictable mild stress‐induced depressive mice by modulating microbiota‐gut‐brain axis

Zhang

Sun

Liu

et al. 2023

Phytotherapy Research

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Polygonum sibiricum polysaccharides (PSP) are one of the main active components of Polygonatum sibiricum, which is a traditional Chinese medicine with food and drug homologies. Recent studies have revealed the antidepressant-like effects of PSP. However, the precise mechanisms have not been clarified. Therefore, the present study was conducted to explore that whether PSP could exert the antidepressant-like effects via microbiota-gut-brain (MGB) axis in chronic unpredictable mild stress (CUMS)-induced depressive mice by transplantation of fecal microbiota (FMT) from PSP administration mice. FMT markedly reversed the depressive-like behaviors of CUMS-induced mice in the open field, the sucrose preference, the tail suspension, the forced swimming, and the novelty-suppressed feeding tests. FMT significantly increased the levels of 5-hydroxytryptamine and norepinephrine, decreased the levels of the pro-inflammatory cytokines in the hippocampus and reduced the levels of corticosterone, an adrenocorticotropic-hormone, in the serum of CUMS-induced mice. In addition, administration of PSP and FMT significantly increased the expressions of ZO-1 and occludin in the colon and decreased the levels of lipopolysaccharide and interferon-γ in the serum of CUMSinduced mice. Moreover, administration of PSP and FMT regulated the signaling pathways of PI3K/AKT/TLR4/NF-κB and ERK/CREB/BDNF. Taken together, these findings indicated that PSP exerted antidepressant-like effects via the MGB axis.

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Section: Discussionmentioning

confidence: 99%

Polygonum sibiricum polysaccharides exert the antidepressant‐like effects in chronic unpredictable mild stress‐induced depressive mice by modulating microbiota‐gut‐brain axis

Zhang

Sun

Liu

et al. 2023

Phytotherapy Research

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“…There was frequent disagreement among the results obtained by different studies, possibly due to preanalytical factors such as acquiring samples, storage and small sample sizes ( 179 ). For instance, studies reported that they controlled inflammatory responses via the inhibition of miR-146a expression ( 173 , 180 ), while for inflammation therapy, miR-146a mimics were delivered in vivo to upregulate miR-146a levels ( 176 ). These principles appear mutually contradictory.…”

Section: Discussionmentioning

confidence: 99%

“…Drugs such as vildagliptin ( 173 ) and GSKJ4 ( 174 ) attenuated inflammation by regulating miR-146a expression. Other studies reported that inhibition of lncRNAs such as XIST ( 175 ) and SNHG16 ( 176 ) suppressed inflammatory responses by sponging miR-146a.…”

Section: Application Strategiesmentioning

confidence: 99%

Mechanisms and application strategies of miRNA‑146a regulating inflammation and fibrosis at molecular and cellular levels (Review)

2022

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In the progression of various diseases, inflammation has a critical role. Chronic persistent inflammation is a pivotal trigger of fibrosis. Several microRNAs (miRNAs) participate in inflammation and fibrosis. In recent years, it has been proved that miRNAs are a critical link in physiological and pathological processes. Among them, the miRNA miR-146a has a pivotal role in the immune system and acquired immunity, making it one of the most studied miRNAs. Due to its essential roles at the molecular and cellular levels, it has broad application prospects in precision medicine. The present comprehensive review focused on the mechanisms of miR-146a and its application strategies in inflammation and fibrosis, discussing its therapeutic potential. The main signaling pathways through which miR-146a regulates inflammation and fibrosis and their relationships were covered. Furthermore, the functions and effects of miR-146a in specific cells, which may join in the process of inflammation and fibrosis, were outlined. Application strategies were also summarized according to recent studies based on these mechanisms. Contents 1. Introduction 2. Location and transcription regulation of miR-146a 3. miR-146a and inflammation 4. miR-146a and fibrosis 5. Application strategies 6. Conclusions and perspectives

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“…Fouad et al generated acetic acid‐induced colitis rats and indirectly stimulated GLP‐1 receptors by vildagliptin, a dipeptidyl peptidase IV (DPPIV) inhibitor that inhibits GLP‐1 degradation [46]. In addition to decreasing disease activity index and phosphorylated PI3K and AKT levels, vildagliptin increased p65 NF‐kB levels in the nuclear fractions of intestinal tissues [47]. Moreover, vildagliptin mitigated the expressions of miR‐146a, as well as long non‐coding RNA interferon gamma antisense 1 (lncRNA IFNG‐AS1) in the enteric tissues [47], two RNAs significantly overexpressed in UC intestines [48, 49].…”

Section: Pi3k Signaling and Ucmentioning

confidence: 99%

“…In addition to decreasing disease activity index and phosphorylated PI3K and AKT levels, vildagliptin increased p65 NF‐kB levels in the nuclear fractions of intestinal tissues [47]. Moreover, vildagliptin mitigated the expressions of miR‐146a, as well as long non‐coding RNA interferon gamma antisense 1 (lncRNA IFNG‐AS1) in the enteric tissues [47], two RNAs significantly overexpressed in UC intestines [48, 49]. The key role of micro RNAs in the pathogenesis of UC and their relationship with PI3K/AKT pathway had previously been shown by Jiang et al [50].…”

Section: Pi3k Signaling and Ucmentioning

confidence: 99%

Phosphatidylinositol 3‐kinase signaling pathway and inflammatory bowel disease: Current status and future prospects

Jalil¹,

Hassan

Abdulameer

et al. 2023

Fundamemntal Clinical Pharma

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Inflammatory bowel disease (IBD) is a chronic life‐limiting disease of gastrointestinal tract characterized by widespread enteric inflammation. IBD is a multifactorial disease, and different environmental, microbial, and immune‐related factors give rise to the development of disease. Among several factors, the preponderance of pro‐inflammatory T helper 17 cells over the anti‐inflammatory regulatory T cells augments inflammation in the intestinal mucosa. Prevailing evidence accentuates that PI3K signaling pathway plays a central role in the pathophysiology of the condition by regulating the inflammatory process in the gut mucosa. By recognizing the implications of PI3K in the pathogenesis of IBD, agents that could modulate this pathway have recently been at the focus of research, yielding encouraging results mainly in the experimental IBD models. In this review, we have summarized the recent advances, which may hold the keys to identify novel therapeutic strategies for IBD.

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Vildagliptin attenuates acetic acid-induced colitis in rats via targeting PI3K/Akt/NFκB, Nrf2 and CREB signaling pathways and the expression of lncRNA IFNG-AS1 and miR-146a

Cited by 24 publications

References 57 publications

Polygonum sibiricum polysaccharides exert the antidepressant‐like effects in chronic unpredictable mild stress‐induced depressive mice by modulating microbiota‐gut‐brain axis

Polygonum sibiricum polysaccharides exert the antidepressant‐like effects in chronic unpredictable mild stress‐induced depressive mice by modulating microbiota‐gut‐brain axis

Mechanisms and application strategies of miRNA‑146a regulating inflammation and fibrosis at molecular and cellular levels (Review)

Phosphatidylinositol 3‐kinase signaling pathway and inflammatory bowel disease: Current status and future prospects

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