Semaglutide, a novel glucagon-like peptide-1 agonist, amends experimental autoimmune encephalomyelitis-induced multiple sclerosis in mice: Involvement of the PI3K/Akt/GSK-3β pathway

Sadek, Mohamed A; Kandil, Esraa A.; Sayed, Nesrine S. El; Sayed, Helmy M.; Rabie, Mostafa A.

doi:10.1016/j.intimp.2022.109647

Cited by 18 publications

(5 citation statements)

References 98 publications

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“…In the present study, co-treatment with either alogliptin or semaglutide ameliorated the coupled upregulation of NF-κB/TNF-α induced by DOX. These results are in accordance with other studies reporting the anti-inflammatory effects of GLP-1RA, semaglutide, in different models, such as obesity, multiple sclerosis, and diabetes ( Tan and Tan, 2019 ; Pan et al, 2023 ; Sadek et al, 2023 ), and the DPP-4 inhibitor, alogliptin, in lipopolysaccharide-induced neuroinflammation ( El-Sahar et al, 2021 ). It is also worth mentioning that alogliptin showed the protective effect against DOX-induced testicular dysfunction through decreasing oxidative stress, inflammation, and apoptosis ( Kabel, 2018 ).…”

Section: Discussionsupporting

confidence: 93%

Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1/Nrf2/NF-κB/TNF-α signaling pathways

Botros,

Matouk,

Amin

et al. 2024

Front. Pharmacol.

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Introduction: Nephrotoxicity represents a major complication of using doxorubicin (DOX) in the management of several types of cancers. Increased oxidative stress and the activation of inflammatory mediators play outstanding roles in the development of DOX-induced kidney damage. This study aimed to investigate whether the two pathways of incretin-based therapy, glucagon-like peptide-1 receptor agonist (presented as semaglutide, SEM) and dipeptidyl peptidase-4 inhibitor (presented as alogliptin, ALO), differentially protect against DOX-induced nephrotoxicity in rats and to clarify the underlying molecular mechanisms.Methods: Adult male rats were divided into six groups: control (received the vehicle), DOX (20 mg/kg, single I.P. on day 8), DOX + ALO (20 mg/kg/day, P.O. for 10 days), DOX + SEM (12 μg/kg/day, S.C. for 10 days), ALO-alone, and SEM-alone groups. At the end of the study, the animals were sacrificed and their kidney functions, oxidative stress, and inflammatory markers were assessed. Kidney sections were also subjected to histopathological examinations.Results: The co-treatment with either ALO or SEM manifested an improvement in the kidney functions, as evidenced by lower serum concentrations of creatinine, urea, and cystatin C compared to the DOX group. Lower levels of MDA, higher levels of GSH, and increased SOD activity were observed in either ALO- or SEM-treated groups than those observed in the DOX group. DOX administration resulted in decreased renal expressions of sirtuin 1 (SIRT1) and Nrf2 with increased NF-κB and TNF-α expressions, and these effects were ameliorated by treatment with either ALO or SEM.Discussion: Co-treatment with either ALO or SEM showed a renoprotective effect that was mediated by their antioxidant and anti-inflammatory effects via the SIRT1/Nrf2/NF-κB/TNF-α pathway. The fact that both pathways of the incretin-based therapy demonstrate an equally positive effect in alleviating DOX-induced renal damage is equally noteworthy.

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Section: Discussionsupporting

confidence: 93%

Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1/Nrf2/NF-κB/TNF-α signaling pathways

Botros,

Matouk,

Amin

et al. 2024

Front. Pharmacol.

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“…Moreover, AMPK activation is known to increase the dissociation of Bcl‐2 from beclin‐1, resulting in the activation of autophagy and the attenuation of apoptosis (He et al, 2013). Furthermore, Bcl‐2 can bind to Bax and thereby inhibit the oligomerization of the apoptotic proteins attenuating apoptosis (Li et al, 2017; Sadek et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Inosine attenuates rotenone‐induced Parkinson's disease in rats by alleviating the imbalance between autophagy and apoptosis

El‐Latif

Rabie

Sayed

et al. 2023

Drug Development Research

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Growing evidence points to impaired autophagy as one of the major factors implicated in the pathophysiology of Parkinson's disease (PD). Autophagy is a downstream target of adenosine monophosphate‐activated protein kinase (AMPK). Inosine has already demonstrated a neuroprotective effect against neuronal loss in neurodegenerative diseases, mainly due its anti‐inflammatory and antioxidant properties. We, herein, aimed at investigating the neuroprotective effects of inosine against rotenone‐induced PD in rats and to focus on the activation of AMPK‐mediated autophagy. Inosine successfully increased p‐AMPK/AMPK ratio in PD rats and improved their motor performance and muscular co‐ordination (assessed by rotarod, open field, and grip strength tests, as well as by manual gait analysis). Furthermore, inosine was able to mitigate the rotenone‐induced histopathological alterations and to restore the tyrosine hydroxylase immunoreactivity in PD rats' substantia nigra. Inosine‐induced AMPK activation resulted in an autophagy enhancement, as demonstrated by the increased striatal Unc‐S1‐like kinase1 and beclin‐1 expression, and also by the increment light chain 3II to light chain 3I ratio, along with the decline in striatal mammalian target of rapamycin and p62 protein expressions. The inosine‐induced stimulation of AMPK also attenuated neuronal apoptosis and promoted antioxidant activity. Unsurprisingly, these neuroprotective effects were antagonized by a preadministration of dorsomorphin (an AMPK inhibitor). In conclusion, inosine exerted neuroprotective effects against the rotenone‐induced neuronal loss via an AMPK activation and through the restoration of the imbalance between autophagy and apoptosis. These findings support potential application of inosine in PD treatment.

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“…As critical regulators of cellular homeostasis, AMPK, an essential energy sensor, and SIRT1, a NAD + ‐dependent deacetylase, contribute to neuroprotection and the modulation of neuroinflammatory responses in AD (Razick et al, 2023). Curcumin demonstrated neuroprotective effects in AD models, partially by modulating the AMPK/SIRT1 pathway; the activation of AMPK and SIRT1 by curcumin results in improved mitochondrial function, decreased oxidative stress, and reduced neuroinflammation, supporting its potential as a therapeutic agent in AD (Sadek et al, 2023). Curcumin's activation of AMPK has been shown to promote autophagy, a critical process for the removal of damaged cellular components and misfolded proteins, including amyloid‐beta and hyperphosphorylated Tau in AD; by stimulating autophagy, curcumin aids in reducing the toxic protein aggregates that contribute to AD pathology (Mishra et al, 2022; Shao et al, 2023).…”

Section: Curcumin and Neuroinflammation In Ad: Protective Molecular M...mentioning

confidence: 99%

Neuroprotective and anti‐inflammatory effects of curcumin in Alzheimer's disease: Targeting neuroinflammation strategies

Azzini,

Peña‐Corona,

Hernández‐Parra

et al. 2024

Phytotherapy Research

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid‐beta plaques and neurofibrillary tangles, leading to neuronal loss. Curcumin, a polyphenolic compound derived from Curcuma longa, has shown potential neuroprotective effects due to its anti‐inflammatory and antioxidant properties. This review aims to synthesize current preclinical data on the anti‐neuroinflammatory mechanisms of curcumin in the context of AD, addressing its pharmacokinetics, bioavailability, and potential as a therapeutic adjunct. An exhaustive literature search was conducted, focusing on recent studies within the last 10 years related to curcumin's impact on neuroinflammation and its neuroprotective role in AD. The review methodology included sourcing articles from specialized databases using specific medical subject headings terms to ensure precision and relevance. Curcumin demonstrates significant neuroprotective properties by modulating neuroinflammatory pathways, scavenging reactive oxygen species, and inhibiting the production of pro‐inflammatory cytokines. Despite its potential, challenges remain regarding its limited bioavailability and the scarcity of comprehensive human clinical trials. Curcumin emerges as a promising therapeutic adjunct in AD due to its multimodal neuroprotective benefits. However, further research is required to overcome challenges related to bioavailability and to establish effective dosing regimens in human subjects. Developing novel delivery systems and formulations may enhance curcumin's therapeutic potential in AD treatment.

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Semaglutide, a novel glucagon-like peptide-1 agonist, amends experimental autoimmune encephalomyelitis-induced multiple sclerosis in mice: Involvement of the PI3K/Akt/GSK-3β pathway

Cited by 18 publications

References 98 publications

Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1/Nrf2/NF-κB/TNF-α signaling pathways

Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1/Nrf2/NF-κB/TNF-α signaling pathways

Inosine attenuates rotenone‐induced Parkinson's disease in rats by alleviating the imbalance between autophagy and apoptosis

Neuroprotective and anti‐inflammatory effects of curcumin in Alzheimer's disease: Targeting neuroinflammation strategies

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