scholarly journals Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia-Induced Neurodegeneration in the Brain and Retina

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Li Pan ◽  
Kin-Sang Cho ◽  
Irvin Yi ◽  
Chi-Ho To ◽  
Dong Feng Chen ◽  
...  

Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).

2017 ◽  
Vol 39 (6) ◽  
pp. 1069-1084 ◽  
Author(s):  
Ranjana Poddar ◽  
Sathyanarayanan Rajagopal ◽  
Lucas Winter ◽  
Andrea M Allan ◽  
Surojit Paul

Extensive research over the last two decades has advanced our understanding of the pathophysiology of ischemic stroke. However, current pharmacologic therapies are still limited to rapid reperfusion using thrombolytic agents, and neuroprotective approaches that can reduce the consequences of ischemic and reperfusion injury, are still not available. To bridge this gap, we have evaluated the long-term efficacy and therapeutic time window of a novel peptide-based neuroprotectant TAT-STEP, derived from the brain-enriched and neuron-specific tyrosine phosphatase STEP. Using a rat model of transient middle cerebral artery occlusion (90 min), we show that a single intravenous administration of the peptide at the onset of reperfusion (early) or 6 h after the onset of the insult (delayed) reduces mortality rate. In the surviving rats, MRI scans of the brain at days 1, 14 and 28 after the insult show significant reduction in infarct size and improvement of structural integrity within the infarcted area following peptide treatment, regardless of the time of administration. Behavioral assessments show significant improvement in normal gait, motor coordination, sensory motor function and spatial memory following early or delayed peptide treatment. The study establishes for the first time the therapeutic potential of a tyrosine phosphatase in ischemic brain injury.


2001 ◽  
Vol 12 (2) ◽  
pp. 361-367
Author(s):  
INGRID H. C. VOS ◽  
TON J. RABELINK ◽  
BERT DORLAND ◽  
REMKO LOOS ◽  
BEN VAN MIDDELAAR ◽  
...  

Abstract. Recovery from ischemia/reperfusion and immune-mediated injury in the renal transplant is associated with reduced renal hemodynamics and increased leukocyte infiltration. In diverse models of renal failure, L-arginine supplementation improved hemodynamics and reduced inflammation. However in a proinflammatory environment, L-arginine can worsen renal injury. This study investigated the therapeutic potential of L-arginine supplementation in allogeneic renal transplantation: Brown Norway rat kidneys were transplanted into Lewis rat recipients, with one native kidney remaining. Recipients received low-dose cyclosporin A (2.5 mg/kg per d subcutaneously) to obtain moderate vascular and interstitial rejection, with or without 1% L-arginine in drinking water for 7 d posttransplantation. Transplantation increased renal vasoconstriction (from 16.9 ± 1.33 to 35.1 ± 8.6 units;P< 0.01), thereby reducing GFR (from 0.96 ± 0.09 to 0.48 ± 0.10 ml/min;P< 0.05). Treatment with L-arginine restored renal graft function to levels found in normal donors (renal vascular resistance, 15.7 ± 1.69 units; GFR, 0.80 ± 0.06 ml/min). L-arginine significantly reduced vascular occlusion because of less inflammation, endothelial disruption, and thrombosis. L-arginine also decreased tubulitis, interstitial injury, and macrophage infiltration. These protective effects suggest that L-arginine might be useful as additive therapy to conventional immune suppression.


2018 ◽  
Vol 25 (14) ◽  
pp. 1663-1681 ◽  
Author(s):  
Chun-Ting Lee ◽  
Heng-Chun Kuo ◽  
Yung-Hsiang Chen ◽  
Ming-Yen Tsai

The polysaccharides in many plants are attracting worldwide attention because of their biological activities and medical properties, such as anti-viral, anti-oxidative, antichronic inflammation, anti-hypertensive, immunomodulation, and neuron-protective effects, as well as anti-tumor activity. Denodrobium species, a genus of the family orchidaceae, have been used as herbal medicines for hundreds of years in China due to their pharmacological effects. These effects include nourishing the Yin, supplementing the stomach, increasing body fluids, and clearing heat. Recently, numerous researchers have investigated possible active compounds in Denodrobium species, such as lectins, phenanthrenes, alkaloids, trigonopol A, and polysaccharides. Unlike those of other plants, the biological effects of polysaccharides in Dendrobium are a novel research field. In this review, we focus on these novel findings to give readers an overall picture of the intriguing therapeutic potential of polysaccharides in Dendrobium, especially those of the four commonly-used Denodrobium species: D. huoshanense, D. offininale, D. nobile, and D. chrysotoxum.


2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jinyoung Kim ◽  
Kihyoun Park ◽  
Min Jung Kim ◽  
Hyejin Lim ◽  
Kook Hwan Kim ◽  
...  

AbstractWe have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP+ mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Conor McQuaid ◽  
Molly Brady ◽  
Rashid Deane

Abstract Background SARS-CoV-2, a coronavirus (CoV), is known to cause acute respiratory distress syndrome, and a number of non-respiratory complications, particularly in older male patients with prior health conditions, such as obesity, diabetes and hypertension. These prior health conditions are associated with vascular dysfunction, and the CoV disease 2019 (COVID-19) complications include multiorgan failure and neurological problems. While the main route of entry into the body is inhalation, this virus has been found in many tissues, including the choroid plexus and meningeal vessels, and in neurons and CSF. Main body We reviewed SARS-CoV-2/COVID-19, ACE2 distribution and beneficial effects, the CNS vascular barriers, possible mechanisms by which the virus enters the brain, outlined prior health conditions (obesity, hypertension and diabetes), neurological COVID-19 manifestation and the aging cerebrovascualture. The overall aim is to provide the general reader with a breadth of information on this type of virus and the wide distribution of its main receptor so as to better understand the significance of neurological complications, uniqueness of the brain, and the pre-existing medical conditions that affect brain. The main issue is that there is no sound evidence for large flux of SARS-CoV-2 into brain, at present, compared to its invasion of the inhalation pathways. Conclusions While SARS-CoV-2 is detected in brains from severely infected patients, it is unclear on how it gets there. There is no sound evidence of SARS-CoV-2 flux into brain to significantly contribute to the overall outcomes once the respiratory system is invaded by the virus. The consensus, based on the normal route of infection and presence of SARS-CoV-2 in severely infected patients, is that the olfactory mucosa is a possible route into brain. Studies are needed to demonstrate flux of SARS-CoV-2 into brain, and its replication in the parenchyma to demonstrate neuroinvasion. It is possible that the neurological manifestations of COVID-19 are a consequence of mainly cardio-respiratory distress and multiorgan failure. Understanding potential SARS-CoV-2 neuroinvasion pathways could help to better define the non-respiratory neurological manifestation of COVID-19.


Author(s):  
Yangjiani Li ◽  
Nathan E. Hall ◽  
Suzann Pershing ◽  
Leslie Hyman ◽  
Julia A. Haller ◽  
...  

2020 ◽  
pp. 108705472096456
Author(s):  
Yue Yang ◽  
Gang Peng ◽  
Hongwu Zeng ◽  
Diangang Fang ◽  
Linlin Zhang ◽  
...  

Objective: The present study aimed to examine the effects of SNAP25 on the integration ability of intrinsic brain functions in children with ADHD, and whether the integration ability was associated with working memory (WM). Methods: A sliding time window method was used to calculate the spatial and temporal concordance among five rs-fMRI regional indices in 55 children with ADHD and 20 healthy controls. Results: The SNAP25 exhibited significant interaction effects with ADHD diagnosis on the voxel-wise concordance in the right posterior central gyrus, fusiform gyrus and lingual gyrus. Specifically, for children with ADHD, G-carriers showed increased voxel-wise concordance in comparison to TT homozygotes in the right precentral gyrus, superior frontal gyrus, postcentral gyrus, and middle frontal gyrus. The voxel-wise concordance was also found to be related to WM. Conclusion: Our findings provided a new insight into the neural mechanisms of the brain function of ADHD children.


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