Nicotinate‐curcumin ameliorates cognitive impairment in diabetic rats by rescuing autophagic flux in CA1 hippocampus

Gu, Hong‐Feng; Li, Na; Tang, Yaling; Yan, Chuan; Shi, Zhe; Yi, Si‐Ni; Zhou, Hao‐Ling; Liao, Duan‐Fang; Ouyang, Xin

doi:10.1111/cns.13059

Cited by 28 publications

(22 citation statements)

References 36 publications

(67 reference statements)

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“…Ischemic lesion volume is an important predictor of functional outcome after stroke with larger lesions corresponding to worse stroke outcome 43,44 . Diabetes and stroke are both known to trigger neuronal apoptosis, and dysregulated apoptosis in the IBZ can contribute to increased cell death and larger infarct area following stroke 44–46 . Ang1 has previously been shown to reduce infarct volume in mice subjected to focal cerebral embolic ischemia 7 .…”

Section: Discussionmentioning

confidence: 99%

Treatment with an Angiopoietin‐1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

et al. 2020

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Aim Vasculotide (VT), an angiopoietin‐1 mimetic peptide, exerts neuroprotective effects in type one diabetic (T1DM) rats subjected to ischemic stroke. In this study, we investigated whether delayed VT treatment improves long‐term neurological outcome after stroke in T1DM rats. Methods Male Wistar rats were induced with T1DM, subjected to middle cerebral artery occlusion (MCAo) model of stroke, and treated with PBS (control), 2 µg/kg VT, 3 µg/kg VT, or 5.5 µg/kg VT. VT treatment was initiated at 24 h after stroke and administered daily (i.p) for 14 days. We evaluated neurological function, lesion volume, vascular and white matter remodeling, and inflammation in the ischemic brain. In vitro, we evaluated the effects of VT on endothelial cell capillary tube formation and inflammatory responses of primary cortical neurons (PCN) and macrophages. Results Treatment of T1DM‐stroke with 3 µg/kg VT but not 2 µg/kg or 5.5 µg/kg significantly improves neurological function and decreases infarct volume and cell death compared to control T1DM‐stroke rats. Thus, 3 µg/kg VT dose was employed in all subsequent in vivo analysis. VT treatment significantly increases axon and myelin density, decreases demyelination, decreases white matter injury, increases number of oligodendrocytes, and increases vascular density in the ischemic border zone of T1DM stroke rats. VT treatment significantly decreases MMP9 expression and decreases the number of M1 macrophages in the ischemic brain of T1DM‐stroke rats. In vitro, VT treatment significantly decreases endothelial cell death and decreases MCP‐1, endothelin‐1, and VEGF expression under high glucose (HG) and ischemic conditions and significantly increases capillary tube formation under HG conditions when compared to non‐treated control group. VT treatment significantly decreases inflammatory factor expression such as MMP9 and MCP‐1 in macrophages subjected to LPS activation and significantly decreases IL‐1β and MMP9 expression in PCN subjected to ischemia under HG conditions. Conclusion Delayed VT treatment (24 h after stroke) significantly improves neurological function, promotes vascular and white matter remodeling, and decreases inflammation in the ischemic brain after stroke in T1DM rats.

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Section: Discussionmentioning

confidence: 99%

Treatment with an Angiopoietin‐1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

et al. 2020

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“…Enhanced autophagy in the hippocampus is reportedly able to improve cognitive impairment in rats . AMPKα1‐induced autophagy is a key mechanism for minocycline to protect neurons from radiation‐induced apoptosis .…”

Section: Discussionmentioning

confidence: 99%

AMPKα1 overexpression improves postoperative cognitive dysfunction in aged rats through AMPK‐Sirt1 and autophagy signaling

Yan

Wang

Ren

et al. 2019

J of Cellular Biochemistry

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Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients who undergo surgery involving anesthesia. Its underlying mechanisms remain unclear. Autophagy plays an important role in the damage and repair of the nervous system and is associated with the development of POCD. Using a rat model, adenosine monophosphate-activated protein kinase α1 (AMPKα1), an important autophagy regulator, was found to be significantly downregulated in rats with POCD that was induced by sevoflurane anesthesia or by appendectomy. Overexpression of AMPKα1-ameliorated POCD, as indicated by decreased escape latencies and increased target quadrant swimming times, swimming distances, and platform crossing times during Morris water maze tests. AMPKα1 overexpression activated autophagy signals by increasing the expression of light chain 3 II (LC3-II) and Beclin1 and decreasing the expression of p62 in the hippocampus of rats with POCD. Moreover, blocking autophagy by 3-methyladenine partly attenuated AMPKα1mediated POCD improvement. Furthermore, overexpression of AMPKα1 could upregulate the expression of p-AMPK and Sirt1 in the hippocampus of rats with POCD. Intriguingly, inhibiting AMPK signals via Compound C effectively attenuated AMPKα1-mediated POCD improvement, concomitant with the downregulation of p-AMPK, Sirt1, LC3-II, and Beclin1 and the upregulation of p62. We thus concluded that overexpression of AMPKα1 can improve POCD via the AMPK-Sirt1 and autophagy signaling pathway. K E Y W O R D S AMPKα1, autophagy, postoperative cognitive dysfunction

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“…Nicotinate-curcumin is a novel derivative of nicotinate and curcumin, with improved water solubility and bioavailability [ 11 ]. Recent studies have reported that NC not only induces HCT116, MCF-7, and CNE2 cell apoptosis and cycle arrest through a P53-mediated mechanism in cancer, but also ameliorates cognitive impairment in diabetic rats [ 23 , 24 ]. Furthermore, NC regulates lipid metabolism, impedes foam cell formation, and inhibits atherosclerosis formation in apoE −/- mice with vascular diseases [ 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Nicotinate-curcumin inhibits AngII-induced vascular smooth muscle cell phenotype switching by upregulating Daxx expression

Sun

Cao

Huo

et al. 2021

Cell Adhesion & Migration

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Phenotypic switching is the main cause of the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). We previously showed that Daxx exerted negative regulatory effect on AngII-induced VSMC proliferation and migration. However, the function of Daxx in VSMC phenotype switching remained unknown. Nicotinate-curcumin (NC) is an esterification derivative of niacin and curcumin that can prevent the formation of atherosclerosis. We found that NC significantly decreased AngII-induced VSMC phenotype switching. Furthermore, NC significantly inhibited AngII-induced cell proliferation and migration. Moreover, NC upregulated Daxx expression and regulated the PTEN/Akt signaling pathway. We concluded that NC inhibited AngII-induced VSMC phenotype switching by regulating the PTEN/Akt pathway, and through a mechanism that might be associated with the upregulation of Daxx expression.

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Nicotinate‐curcumin ameliorates cognitive impairment in diabetic rats by rescuing autophagic flux in CA1 hippocampus

Abstract: These results indicate that NC ameliorates DM-induced cognitive function impairment via restoring autophagic flux might by inhibiting mTOR/p70S6k activation in the CA1 region, and NC may be a promising agent for diabetic cognitive dysfunction prevention and treatment.

Cited by 28 publications

References 36 publications

Treatment with an Angiopoietin‐1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

Treatment with an Angiopoietin‐1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

AMPKα1 overexpression improves postoperative cognitive dysfunction in aged rats through AMPK‐Sirt1 and autophagy signaling

Nicotinate-curcumin inhibits AngII-induced vascular smooth muscle cell phenotype switching by upregulating Daxx expression

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