scholarly journals A Review of Plant Extracts and Plant-Derived Natural Compounds in the Prevention/Treatment of Neonatal Hypoxic-Ischemic Brain Injury

2021 ◽  
Vol 22 (2) ◽  
pp. 833
Author(s):  
Hadi Mohsenpour ◽  
Mirko Pesce ◽  
Antonia Patruno ◽  
Azam Bahrami ◽  
Pardis Mohammadi Pour ◽  
...  
Keyword(s):  
Brain Injury ◽  
Brain Damage ◽  
Plant Extracts ◽  
Molecular Mechanisms ◽  
Newborn Infants ◽  
Natural Compounds ◽  
Neurological Dysfunction ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
Natural Agents

Neonatal hypoxic-ischemic (HI) brain injury is one of the major drawbacks of mortality and causes significant short/long-term neurological dysfunction in newborn infants worldwide. To date, due to multifunctional complex mechanisms of brain injury, there is no well-established effective strategy to completely provide neuroprotection. Although therapeutic hypothermia is the proven treatment for hypoxic-ischemic encephalopathy (HIE), it does not completely chang outcomes in severe forms of HIE. Therefore, there is a critical need for reviewing the effective therapeutic strategies to explore the protective agents and methods. In recent years, it is widely believed that there are neuroprotective possibilities of natural compounds extracted from plants against HIE. These natural agents with the anti-inflammatory, anti-oxidative, anti-apoptotic, and neurofunctional regulatory properties exhibit preventive or therapeutic effects against experimental neonatal HI brain damage. In this study, it was aimed to review the literature in scientific databases that investigate the neuroprotective effects of plant extracts/plant-derived compounds in experimental animal models of neonatal HI brain damage and their possible underlying molecular mechanisms of action.

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

2020 ◽  
Vol 28 (2) ◽  
pp. 360-376 ◽  
Author(s):  
Atefeh Amiri ◽  
Maryam Mahjoubin-Tehran ◽  
Zatollah Asemi ◽  
Alimohammad Shafiee ◽  
Sarah Hajighadimi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Antioxidant Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Therapeutic Modalities ◽  
Anti Cancer ◽  
Current Therapies ◽  
Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

Novel Synthetic and Natural Therapies for Traumatic Brain Injury

2021 ◽  
Vol 19 ◽  
Author(s):  
Denise Battaglini ◽  
Dorota Siwicka-Gieroba ◽  
Patricia RM Rocco ◽  
Fernanda Ferreira Cruz ◽  
Pedro Leme Silva ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Damage ◽  
Molecular Mechanisms ◽  
Antioxidant Properties ◽  
Secondary Brain Injury ◽  
Specific Recommendation ◽  
Novel Therapies ◽  
Secondary Brain Damage ◽  
Late Treatment

: Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages and cellular necrosis that is followed by a dynamic secondary brain damage that presumably results in additional destruction of the brain. In order to minimize deleterious consequences of the secondary brain damage-such as inflammation, bleeding or reduced oxygen supply. The old concept of the -staircase approach- has been updated in recent years by most guidelines and should be followed as it is considered the only validated approach for the treatment of TBI. Besides, a variety of novel therapies have been proposed as neuroprotectants. The molecular mechanisms of each drug involved in inhibition of secondary brain injury can result as potential target for the early and late treatment of TBI. However, no specific recommendation is available on their use in clinical setting. The administration of both synthetic and natural compounds, which act on specific pathways involved in the destructive processes after TBI, even if usually employed for the treatment of other diseases, can show potential benefits. This review represents a massive effort towards current and novel therapies for TBI that have been investigated in both pre-clinical and clinical settings. This review aims to summarize the advancement in therapeutic strategies basing on specific and distinct -target of therapies-: brain edema, ICP control, neuronal activity and plasticity, anti-inflammatory and immunomodulatory effects, cerebral autoregulation, antioxidant properties, and future perspectives with the adoption of mesenchymal stromal cells.

scholarly journals Comparative Neuroprotective Effects of Cyclosporin a and NIM811, a Nonimmunosuppressive Cyclosporin a Analog, following Traumatic Brain Injury

2008 ◽  
Vol 29 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Lamin Han Mbye ◽  
Indrapal N Singh ◽  
Kimberly M Carrico ◽  
Kathryn E Saatman ◽  
Edward D Hall
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cyclosporin A ◽  
Mitochondrial Dysfunction ◽  
Motor Function ◽  
Neurological Dysfunction ◽  
Neuroprotective Effects ◽  
Function Impairment ◽  
Calcineurin Inhibition ◽  
Experimental Traumatic Brain Injury

Earlier experiments have shown that cyclosporin A (CsA) and its non-calcineurin inhibitory analog NIM811 attenuate mitochondrial dysfunction after experimental traumatic brain injury (TBI). Presently, we compared the neuroprotective effects of previously determined mitochondrial protective doses of CsA (20 mg/kg intraperitoneally) and NIM811 (10 mg/kg intraperitoneally) when administered at 15 mins postinjury in preventing cytoskeletal (α-spectrin) degradation, neuro-degeneration, and neurological dysfunction after severe (1.0 mm) controlled cortical impact (CCI) TBI in mice. In a first set of experiments, we analyzed calpain-mediated α-spectrin proteolysis at 24 h postinjury. Both NIM811 and CsA significantly attenuated the increased α-spectrin breakdown products observed in vehicle-treated animals ( P < 0.005). In a second set of experiments, treatment of animals with either NIM811 or CsA at 15 mins and again at 24 h postinjury attenuated motor function impairment at 48 h and 7 days ( P < 0.005) and neurodegeneration at 7 days postinjury ( P < 0.0001). Delayed administration of NIM811 out to 12 h was still able to significantly reduce α-spectrin degradation. These results show that the neuroprotective mechanism of CsA involves maintenance of mitochondrial integrity and that calcineurin inhibition plays little or no role because the non-calcineurin inhibitory analog, NIM811, is as effective as CsA.

scholarly journals THE NEW STIMULATING METHOD IN THE SPEECH THERAPY WORKOUT SYSTEM FOR THE RESTORATION OF THE SWALLOWING FUNCTION IN SEVERE BRAIN INJURIES

2020 ◽  
pp. 315-321
Author(s):  
Nataly I. Pryanikova
Keyword(s):  
Brain Injury ◽  
Brain Damage ◽  
Tactile Stimulation ◽  
Speech Therapy ◽  
Early Stage ◽  
New Method ◽  
Therapeutic Effects ◽  
Severe Brain Injury ◽  
Swallowing Function ◽  
Positive Effects

Background. The significance of this study becomes more relevant due to the higher incidence and complication of dysphagia in patients with severe brain damage as a result of stroke, traumatic brain injury, and other diseases and injuries. Purpose The study aimed to assess the effectiveness of the new stimulating method - "passive-active logopedic cryomassage" for restoring impaired swallowing function (dysphagia) in patients with severe brain injury, used in the system of speech therapy measures at the early stage of rehabilitation in the neurointensive care unit. Methods. The study involved 96 patients with dysphagia caused by severe brain damage, who received speech therapy assistance aimed at restoring the impaired swallowing function in a system of early rehabilitation measures carried out in a neurorehabilitation department. The severity of dysphagia was evaluated using an integrative assessment of swallowing function scale. Results. The practice of using the new method developed in combination with thermal and tactile stimulation: "passive-active logopedic cryomassage" indicated its higher efficiency in comparison with the traditionally used methods of speech therapy stimulation. In the course of this study, there were three categories of patients: patients with a rapid positive effect, patients with a delayed effect, and patients with no apparent positive effects. There was an analysis of all possible causes of different therapeutic effects. Conclusion. This new method of combined thermal and tactile stimulation - "passive-active logopedic cryomassage" can be recommended with all its indications and contraindications for widespread use in the clinical practice assisting speech therapists in the restoration of impaired swallowing function in patients with severe brain injury

scholarly journals Targeting Autophagy with Natural Compounds in Cancer: A Renewed Perspective from Molecular Mechanisms to Targeted Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiang Xie ◽  
Yi Chen ◽  
Huidan Tan ◽  
Bo Liu ◽  
Ling-Li Zheng ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Therapy ◽  
Signaling Pathways ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Therapeutic Benefits ◽  
Small Molecule Drugs

Natural products are well-characterized to have pharmacological or biological activities that can be of therapeutic benefits for cancer therapy, which also provide an important source of inspiration for discovery of potential novel small-molecule drugs. In the past three decades, accumulating evidence has revealed that natural products can modulate a series of key autophagic signaling pathways and display therapeutic effects in different types of human cancers. In this review, we focus on summarizing some representative natural active compounds, mainly including curcumin, resveratrol, paclitaxel, Bufalin, and Ursolic acid that may ultimately trigger cancer cell death through the regulation of some key autophagic signaling pathways, such as RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, AMPK, ULK1, Beclin-1, Atg5 and p53. Taken together, these inspiring findings would shed light on exploiting more natural compounds as candidate small-molecule drugs, by targeting the crucial pathways of autophagy for the future cancer therapy.

scholarly journals Young plasma ameliorates aging-related acute brain injury after intracerebral hemorrhage

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Jun-Jie Yuan ◽  
Qin Zhang ◽  
Chang-Xiong Gong ◽  
Fa-Xiang Wang ◽  
Jia-Cheng Huang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Brain Damage ◽  
Mrna Level ◽  
Acute Brain Injury ◽  
Aging Brain ◽  
Neural Cells ◽  
Neuroprotective Effects ◽  
The Brain ◽  
Brain Tissues

Abstract Aging has been shown to contribute to both the declined biofunctions of aging brain and aggravation of acute brain damage, and the former could be reversed by young plasma. These results suggest that young plasma treatment may also reduce the acute brain damage induced by intracerebral hemorrhage (ICH). In the present study, we first found that the administration of young plasma significantly reduced the mortality and neurological deficit score in aging ICH rodents, which might be due to the decreased brain water content, damaged neural cells, and increased survival neurons around the perihematomal brain tissues. Then, proteomics analysis was used to screen out the potential neuroprotective circulating factors and the results showed that many factors were changed in health human plasma among young, adult, and old population. Among these significantly changed factors, the plasma insulin-like growth factor 1 (IGF-1) level was significantly decreased with age, which was further confirmed both in human and rats detected by ELISA. Additionally, the brain IGF-1 protein level in aging ICH rats was markedly decreased when compared with young rats. Interestingly, the relative decreased brain IGF-1 level was reversed by the treatment of young plasma in aging ICH rats, while the mRNA level was non-significantly changed. Furthermore, the IGF-1 administration significantly ameliorated the acute brain injury in aging ICH rats. These results indicated that young circulating factors, like IGF-1, may enter brain tissues to exert neuroprotective effects, and young plasma may be considered as a novel therapeutic approach for the clinical treatment of aging-related acute brain injury.

1,8-cineole ameliorates ischaemic brain damage via TRPC6/CREB pathways in rats

2021 ◽  
Author(s):  
Chen Meng ◽  
Wenjing Zeng ◽  
Jing Lv ◽  
Yu Wang ◽  
Meiling Gao ◽  
...  
Keyword(s):  
Brain Damage ◽  
Transient Receptor Potential ◽  
Infarct Volume ◽  
Glucose Deprivation ◽  
Neurological Dysfunction ◽  
Male Rats ◽  
Neuroprotective Effects ◽  
Ischaemic Brain

Abstract Objectives A previous in vitro study reported that the monoterpene oxide 1,8-cineole (cineole) attenuates neuronal caused by oxygen–glucose deprivation/reoxygenation in culture. However, to date, there is no in vivo evidence showing neuroprotective effects of cineole against stroke. This study aimed to investigate whether cineole attenuates cerebral ischaemic damage in rats. Methods A rat model of middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion was applied. Male rats were treated with oral cineole (100 mg/kg) for 7 consecutive days, then subjected to MCAO surgery. Infarct volume, neurologic deficits, apoptosis and expression levels of all-spectrin breakdown products of 145 kDa (SBDP145), transient receptor potential canonical (subtype) 6 (TRPC6) and phosphorylated CREB (p-CREB) were measured in ischaemic brain tissues. Key findings Cineole treatment significantly reduced infarct volume, neurological dysfunction, neuronal apoptosis, SBDP145 formation and TRPC6 degradation and enhanced p-CREB expression in MCAO rats compared with vehicle treatment. These neuroprotective effects were markedly suppressed by pharmacological inhibition of MEK or CaMKIV signalling. Conclusions Our study provides in vivo evidence demonstrating that cineole pretreatment attenuates ischaemic stroke-induced brain damage, mainly through blocking calpain-induced TRPC6 degradation and activating CREB via MEK/CREB and CaMKIV/CREB signalling pathways.

scholarly journals Oxidative Stress in Intracerebral Hemorrhage: Sources, Mechanisms, and Therapeutic Targets

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Xin Hu ◽  
Chuanyuan Tao ◽  
Qi Gan ◽  
Jun Zheng ◽  
Hao Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Brain Damage ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Heme Iron ◽  
Mortality And Morbidity ◽  
Underlying Mechanisms ◽  
Damaging Effects

Intracerebral hemorrhage (ICH) is associated with the highest mortality and morbidity despite only constituting approximately 10–15% of all strokes. Complex underlying mechanisms consisting of cytotoxic, excitotoxic, and inflammatory effects of intraparenchymal blood are responsible for its highly damaging effects. Oxidative stress (OS) also plays an important role in brain injury after ICH but attracts less attention than other factors. Increasing evidence has demonstrated that the metabolite axis of hemoglobin-heme-iron is the key contributor to oxidative brain damage after ICH, although other factors, such as neuroinflammation and prooxidases, are involved. This review will discuss the sources, possible molecular mechanisms, and potential therapeutic targets of OS in ICH.

scholarly journals AXL kinase-mediated astrocytic phagocytosis modulates outcomes of traumatic brain injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Hang Zhou ◽  
Libin Hu ◽  
Jianru Li ◽  
Wu Ruan ◽  
Yang Cao ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Molecular Mechanisms ◽  
Therapeutic Interventions ◽  
Neurological Dysfunction ◽  
Transmission Electron ◽  
Cultured Astrocytes ◽  
Bv2 Cells

Abstract Background Complex changes in the brain microenvironment following traumatic brain injury (TBI) can cause neurological impairments for which there are few efficacious therapeutic interventions. The reactivity of astrocytes is one of the keys to microenvironmental changes, such as neuroinflammation, but its role and the molecular mechanisms that underpin it remain unclear. Methods Male C57BL/6J mice were subjected to the controlled cortical impact (CCI) to develop a TBI model. The specific ligand of AXL receptor tyrosine kinase (AXL), recombinant mouse growth arrest-specific 6 (rmGas6) was intracerebroventricularly administered, and selective AXL antagonist R428 was intraperitoneally applied at 30 min post-modeling separately. Post-TBI assessments included neurobehavioral assessments, transmission electron microscopy, immunohistochemistry, and western blotting. Real-time polymerase chain reaction (RT-PCR), siRNA transfection, and flow cytometry were performed for mechanism assessments in primary cultured astrocytes. Results AXL is upregulated mainly in astrocytes after TBI and promotes astrocytes switching to a phenotype that exhibits the capability of ingesting degenerated neurons or debris. As a result, this astrocytic transformation promotes the limitation of neuroinflammation and recovery of neurological dysfunction. Pharmacological inhibition of AXL in astrocytes significantly decreased astrocytic phagocytosis both in vivo and in primary astrocyte cultures, in contrast to the effect of treatment with the rmGas6. AXL activates the signal transducer and activator of the transcription 1 (STAT1) pathway thereby further upregulating ATP-binding cassette transporter 1 (ABCA1). Moreover, the supernatant from GAS6-depleted BV2 cells induced limited enhancement of astrocytic phagocytosis in vitro. Conclusion Our work establishes the role of AXL in the transformation of astrocytes to a phagocytic phenotype via the AXL/STAT1/ABCA1 pathway which contributes to the separation of healthy brain tissue from injury-induced cell debris, further ameliorating neuroinflammation and neurological impairments after TBI. Collectively, our findings provide a potential therapeutic target for TBI.

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