scholarly journals Protective effects of essential oil from Fructus Alpiniae zerumbet on retinal Müller gliosis via the PPAR-γ-p-CREB signaling pathway

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Hong Yang ◽  
Shiquan Gan ◽  
Zhaohui Jiang ◽  
Xiaomei Song ◽  
Tingting Chen ◽  
...  
Keyword(s):  
Essential Oil ◽  
Signaling Pathway ◽  
Vision Loss ◽  
Umbilical Vein ◽  
Ectopic Expression ◽  
Müller Cell ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Ppar Γ ◽  
Muller Cell

Abstract Background Diabetic retinopathy (DR) involves extensive retinal damage and is one of the most common and serious complications of diabetes mellitus. Hyperglycemia is the major pathological trigger for diabetic complications. Müller cell gliosis, a key pathophysiological process in DR, could finally lead to vision loss. Our previous finding revealed that the essential oil of Fructus Alpiniae zerumbet (EOFAZ) protects human umbilical vein endothelial cells (HUVECs) against high glucose (HG)-induced injury via the PPAR-γ signal. However, Whether EOFAZ could prevent HG-induced Müller cell gliosis through the PPAR signaling remains unclear. Methods The neuroprotective effects of EOFAZ were evaluated in HG-treated rat retinal Müller cells (RMCs) and DR rat model. Result GFAP and VEGF upregulation is the biomarker of Müller glial reactivity gliosis. Results suggested that EOFAZ could remarkably ameliorate retinal reactive gliosis by suppressing p-CREB and GFAP and VEGF downstream effectors. Its effects on PPAR-γ, a major target for currently available anti-diabetes drugs, were also investigated. EOFAZ treatment remarkably attenuated the reduction of PPAR-γ and high level of p-CaMK II and p-CREB in HG-treated RMCs and diabetic rats. Furthermore, the activation and ectopic expression of PPAR-γ downregulated p-CREB and p-CaMK II in HG-treated RMCs. By contrast, CaMK II inhibitor KN93 and CREB gene silencing did not significantly affect the PPAR-γ expression. Conclusions A novel PPAR-γ-p-CREB signaling pathway accounts for the inhibitory effect of EOFAZ on RMCs gliosis. These findings provide scientific evidence for the potential use of EOFAZ as a complementary and alternative medicine for DR prevention and treatment in the future.

scholarly journals Lipin1 Is Involved in the Pathogenesis of Diabetic Encephalopathy through the PKD/Limk/Cofilin Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Min Xie ◽  
Meijian Wang ◽  
Wei Liu ◽  
Min Xu ◽  
Pan Shang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Type I Diabetes ◽  
Type I ◽  
Protective Effects ◽  
Diabetic Encephalopathy ◽  
Neuroprotective Effects ◽  
Lim Kinase ◽  
Ca1 Region

Diabetic encephalopathy is a type of central diabetic neuropathy resulting from diabetes mainly manifested as cognitive impairments. However, its underlying pathogenesis and effective treatment strategies remain unclear. In the present study, we investigated the effect of Lipin1, a phosphatidic acid phosphatase enzyme, on the pathogenesis of diabetic encephalopathy. We found that in vitro, Lipin1 exerts protective effects on high glucose-induced reductions of PC12 cell viability, while in vivo, Lipin1 is downregulated within the CA1 hippocampal region in a type I diabetes rat model. Increased levels of Lipin1 within the CA1 region are accompanied with protective effects including amelioration of dendritic spine and synaptic deficiencies, phosphorylation of the synaptic plasticity-related proteins, LIM kinase 1 (p-limk1) and cofilin, as well as increases in the synthesis of diacylglycerol (DAG), and the expression of phosphorylated protein kinase D (p-PKD). These effects are associated with the rescue of cognitive disorders as shown in this rat model of diabetes. In contrast, knockdown of Lipin1 within the CA1 region enhanced neuronal abnormalities and the genesis of cognitive impairment in rats. These results suggest that Lipin1 may exert neuroprotective effects involving the PKD/Limk/Cofilin signaling pathway and may serve as a potential therapeutic target for diabetic encephalopathy.

scholarly journals Spontaneous closure of degenerative lamellar macular hole with epiretinal membrane proliferation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rony C. Preti ◽  
Leandro C. Zacharias ◽  
Leonardo P. Cunha ◽  
Mario L. R. Monteiro ◽  
David Sarraf
Keyword(s):  
Macular Hole ◽  
Epiretinal Membrane ◽  
Vision Loss ◽  
Surgical Intervention ◽  
Spontaneous Closure ◽  
Müller Cell ◽  
Lamellar Macular Hole ◽  
Cystic Fluid ◽  
Muller Cell ◽  
Sd Oct

Abstract Background To describe the spontaneous closure of a degenerative lamellar macular hole with epiretinal proliferation (LHEP) as documented with tracked spectral domain optical coherence tomography (SD-OCT). Case presentation A 54-years-old diabetic female patient presented with progressive vision loss in the left eye. SD-OCT illustrated LHEP associated with cystic fluid in the outer nuclear layer. Sequentially tracked SD-OCT showed progressive closure of the degenerative lamellar macular hole and resolution of the CME over almost 4 years, in the absence of any surgical intervention. Discussion/conclusion LHEP may represent a specialized form of degenerative epiretinal membrane associated with Muller cell activation. Spontaneous degenerative LMH closure may rarely occur with these lesion types, in the absence of surgical intervention, possibly due to Muller cell proliferation preceded by PVD.

scholarly journals DL0410 Alleviates Memory Impairment in D-Galactose-Induced Aging Rats by Suppressing Neuroinflammation via the TLR4/MyD88/NF-κB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-31
Author(s):  
Baoyue Zhang ◽  
Wenwen Lian ◽  
Jun Zhao ◽  
Zhe Wang ◽  
Ailin Liu ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Signaling Pathway ◽  
Oxidation Products ◽  
Inflammatory Factors ◽  
Morris Water Maze Test ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Aging Rats ◽  
Bv2 Cells ◽  
Bv2 Microglia

Oxidative stress and neuroinflammation have been demonstrated to be linked with Alzheimer’s disease (AD). In this study, we examined the protective effects of DL0410 in aging rats and explored the underlying mechanism against oxidative damage and neuroinflammation, which was then validated in LPS-stimulated BV2 microglia. We firstly investigated the improvement effects of DL0410 on learning and memory abilities and explored the potential mechanisms in D-gal-induced aging rats. An 8-week treatment with DL0410 significantly improved the learning and cognitive function of D-gal-stimulated Alzheimer’s-like rats in the Morris water maze test, step-down test, and novel object recognition test, and the therapeutic effect of DL0410 at 10 mg/kg was even better than that of donepezil. What is more, the results showed that DL0410 alleviated neuron injury, increased the number of synapses, and improved the level of postsynaptic density protein 95 (PSD95) in the hippocampus and cortex. Next, we examined the protective effects of DL0410 against oxidative damage and neuroinflammation. Our observations indicated that DL0410 reduced the production of harmful oxidation products and promoted the antioxidative system, decreased the levels of proinflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6), and increased anti-inflammatory cytokines IL-10. Moreover, DL0410 inhibited the activation of astrocytes and microglia and suppressed the activation of the TLR4/MyD88/NF-κB signaling pathway. The anti-inflammation effect of DL0410 was further confirmed in LPS-stimulated BV2 cells, and the results showed that DL0410 reduced the level of inflammatory factors and inhibited the activation of the TLR4/MyD88/TRAF6/NF-κB signaling pathway in BV2 microglia. Molecular docking results indicated that DL0410 occupied the LPS recognition site in the TLR4/MD2 complex. Furthermore, the enhanced expression of claudin-1, claudin-5, occludin, CX43, and ZO-1 indicated that DL0410 protected the blood-brain barrier (BBB) integrity. Together, these results suggest that DL0410 exerts neuroprotective effects against hippocampus and cortex injury induced by D-galactose, and the possible mechanisms include antioxidative stress, antineuroinflammation, improving synaptic plasticity, and maintaining BBB integrity, which is mediated by the TLR4/MyD88/NF-κB signaling pathway inhibition. We suggest that DL0410 is a promising candidate for AD treatment.

scholarly journals Dihydromyricetin alleviates endothelial inflammatory response through IRE1α/NF-κB signaling pathway in sepsis

2021 ◽  
Author(s):  
Xifeng Wang ◽  
Xiaomin Xu ◽  
Yu peng Yang ◽  
Xin Xin ◽  
Zekang Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Inflammatory Response ◽  
Er Stress ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Cecal Ligation ◽  
Protective Effects ◽  
Necrosis Factor Alpha

IntroductionThe high mortality of sepsis is closely related to disorder of coagulation induced by endothelial inflammatory response. Our aim is to investigate the protective effects of Dihydromyricetin (DHM) on endothelial cells in sepsis and the endoplasmic reticulum (ER) stress mechanism.Material and methodsIn vivo, we conducted an animal study for which fifty male Wistar rats were randomly and equally divided into five groups: sham group, cecal ligation and puncture (CLP) group and three CLP+ DHM (50, 100, 150 mg/kg) groups, the DHM was orally administered 2 h after CLP for 3 days (once per day). In vitro, human umbilical vein endothelial cells (HUVECs) were treated with DHM (50μmol) for 24 h after stimulation by lipopolysaccharide (LPS). In the inhibition groups, reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC, 3 mmol) and endoplasmic reticulum (ER) stress inhibitor (STF-083010, 10 μmol) were incubated prior to LPS.ResultsOur results indicated that DHM (150 mg/kg) alleviated the histopathological injury of endothelium, decreased the release of inflammatory cytokines and adhesion molecules such as interleukin-1β (IL-1β), interleukin-6 (IL-6) , tumor necrosis factor alpha (TNF-α), vascular cell adhesion molecule 1 (VCAM-1) and endothelin-1 (ET-1), and inhibited the production of ROS production. In addition, we found that DHM ameliorated ER damage, significantly decreased the protein expressions of IRE1α/NF-κB signaling pathway.ConclusionsDHM treatment alleviated inflammatory response of endothelial cells in sepsis through the IRE1α/NF-κB signaling pathway triggered by oxidative stress. This study provided experimental rationale for the treatment of DHM on therapy of sepsis.

The protective effects of activating Sirt1/NF-κB pathway for neurological disorders

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yanhong Song ◽  
Ziyi Wu ◽  
Ping Zhao
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Nuclear Factor Κb ◽  
Vital Role ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Relevant Evidence ◽  
Almost All

Abstract Sirt1, a member of the sirtuins family, is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase. It can be involved in the regulation of several processes including inflammatory response, apoptosis, oxidative stress, energy metabolism, and autophagy by exerting deacetylation. Nuclear factor-κB (NF-κB), a crucial nuclear transcription factor with specific DNA binding sequences, exists in almost all cells and plays a vital role in several biological processes involving inflammatory response, immune response, and apoptosis. As the hub of multiple intracellular signaling pathways, the activity of NF-κB is regulated by multiple factors. Sirt1 can both directly deacetylate NF-κB and indirectly through other molecules to inhibit its activity. We would like to emphasize that Sirt1/NF-κB is a signaling pathway that is closely related to neuroinflammation. Many recent studies have demonstrated the neuroprotective effects of Sirt1/NF-κB signaling pathway activation applied to the treatment of neurological related diseases. In this review, we focus on new advances in the neuroprotective effects of the Sirt1/NF-κB pathway. First, we briefly review Sirt1 and NF-κB, two key molecules of cellular metabolism. Next, we discuss the connection between NF-κB and neuroinflammation. In addition, we explore how Sirt1 regulates NF-κB in nerve cells and relevant evidence. Finally, we analyze the therapeutic effects of the Sirt1/NF-κB pathway in several common neuroinflammation-related diseases.

scholarly journals Protective Effects of Matrine on Acute Myocardial Hypertrophy Induced by Isoproterenol via Akt/mTOR/p70S6K/eIF4E Signaling Pathway in Rats

2021 ◽  
Author(s):  
Hui Ma ◽  
Hongwan Dang ◽  
Shijie Wei ◽  
Xiaoying Yang ◽  
Wenping Zhang
Keyword(s):  
Signaling Pathway ◽  
Myocardial Hypertrophy ◽  
Protective Effects ◽  
Hemodynamic Parameters ◽  
Sprague Dawley ◽  
Chain Reaction ◽  
Neuroprotective Effects ◽  
Mechanistic Target Of Rapamycin ◽  
Sprague Dawley Rats ◽  
Polymerase Chain

AbstractThis study aimed to investigate whether matrine (Ma) attenuates isoproterenol (ISO)-induced acute myocardial hypertrophy via activating Akt/mTOR/p70S6K/eIF4E signaling pathway in rats. We collected 42 male Sprague–Dawley rats weighing 300±20g, randomly divided into seven groups (n=6). The myocardial hypertrophy (MH) model was well established by 85 mg/kg ISO. Changes in hemodynamic parameters were recorded using electrocardiogram after 24h with ISO injection. Western blot and real-time polymerase chain reaction were used to evaluate the expression of Akt, mechanistic target of rapamycin (mTOR), p70S6K, and eIF4E. Tissue arrangement of the 200 and 100 mg/kg Ma+ISO groups was regularly smaller than that of the ISO group. For the protein expression, Akt values in the 200 and 100 mg/kg Ma+ISO groups were 1.57- and 1.81-fold higher than in the ISO group, respectively. Moreover, compared with the ISO group, the expression trends of mTOR in the 200, 100, and 50 mg/kg Ma+ISO groups significantly downregulated. The levels of p70S6K and eIF4E reduced in the 200, 100, and 50 mg/kg Ma+ISO groups according to the ISO group (P<0.05). MRNA expression of p70S6K and eIF4E in the ISO group were 1.90- and 6.38-fold higher compared with that in the 100 mg/kg Ma+ISO group. Ma exerted neuroprotective effects against pachyntic injury. Akt activity was accelerated, but activities of mTOR, p70S6K, and eIF4E were inhibited by Ma. Activation of the Akt/mTOR/p70S6K/eIF4E signaling pathway might be the targets for the protective effects of Ma on acute myocardial hypertrophy in rats.

Demonstration of Retinal Glycogen with Silver Methenamine

1971 ◽  
Vol 29 ◽  
pp. 564-565
Author(s):  
A. W. Sedar ◽  
G. H. Bresnick
Keyword(s):  
Lactic Acid ◽  
Chromic Acid ◽  
Periodic Acid ◽  
Müller Cell ◽  
External Limiting Membrane ◽  
Electron Microscope Level ◽  
Reactive Process ◽  
Inner Limiting Membrane ◽  
Muller Cell ◽  
And Migration

After experimetnal damage to the retina with a variety of procedures Müller cell hypertrophy and migration occurs. According to Kuwabara and others the reactive process in these injuries is evidenced by a marked increase in amount of glycogen in the Müller cells. These cells were considered originally supporting elements with fiber processes extending throughout the retina from inner limiting membrane to external limiting membrane, but are known now to have high lactic acid dehydrogenase activity and the ability to synthesize glycogen. Since the periodic acid-chromic acid-silver methenamine technique was shown to demonstrate glycogen at the electron microscope level, it was selected to react with glycogen in the fine processes of the Müller cell that ramify among the neural elements in various layers of the retina and demarcate these cells cytologically. The Rhesus monkey was chosen as an example of a well vascularized retina and the rabbit as an example of a avascular retina to explore the possibilities of the technique.

Appraisal of in vitro neuroprotective effects of Turkish Pinus L. species and pycnogenol and essential oil analyses

Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
O Ustun ◽  
F Senol ◽  
M Kürkçüoğlu ◽  
I Orhan ◽  
M Kartal ◽  
...  
Keyword(s):  
Essential Oil ◽  
Neuroprotective Effects
Sign in / Sign up

Export Citation Format

Share Document