Solanum melongena extract supplementation protected skeletal muscle and brain damage by regulation of BDNF/PGC1α/irisin pathway via brain function-related myokines in high-fat diet induced obese mice.

In this study, we investigated the protective effects of SM on skeletal muscle and brain damage by regulation of BDNF/PGC1α/irisin pathway via brain function related myokines in high-fat diet-induced OB mice. OB was induced by high-fat diet for 6 weeks. SM extract (SME) was administered with 200 mg/kg BW (LSM) and 500 mg/kg BW (HSM) by oral gavage every day for 12 weeks. Behavior tests such as grip strength, Y-maze, and passive avoidance test were conducted to analyze muscle and cognitive function. Histopathological changes in skeletal muscle and brain were examined by hematoxylin and eosin staining and the protein levels of biomarkers related to oxidative stress, inflammation, protein degradation, neuro-plasticity, and cell cycling were measured by western blot. SME regulated morphological changes (muscle cross-sectional area: 1.23%, 1.40%; density of neurons in hippocampus:1.74%, 1.73%) in T2DM mice. Importantly, SME supplementation significantly increased several muscle-derived myokines which might influence the expression of neuronal markers in OB mice (FGF21: 1.27%, 1.34%; PGC1α: 1.0%, 1.32%; IRISIN: 1.9%, 1.08%; BDNF: 1.35%, 1.23%). Accordingly, SME activated hippocampal neurotrophic factors including BDNF (1.0%, 1.2%) and its associated PGC1α/irisin pathway (PGC1α :1.1%, 1.1%; IRISIN:1.1%, 0.9%) significantly. This study demonstrated the possibliy that protective myokines increased by SME supplementation may contribute to neuro-protection in OB mice. Taken together, the current study suggests that SME can be used to prevent skeletal muscle and brain damage in OB by protecting against oxidative stress and inflammatin via modulation of the BDNF/PGC1α/irisin pathway in the therapeutic approach of obese patients.

Mesenchymal stem cells differentiate to retinal ganglion-like cells in rat glaucoma model induced by polystyrene microspheres.

AIM: The study aimed to evaluate the differentiation ability of intravitreally injected rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) to retinal ganglion-like cells in a polystyrene microsphere induced rat glaucoma model. MATERIALS AND METHODS: The glaucoma rat model was generated via intracameral injection of 7 microliter polystyrene microspheres. Green fluorescence protein-labeled (GFP) rBM-MSCs were transplanted intravitreally at or after induction of ocular hypertension (OHT), depending on the groups. By the end of the fourth week, flat-mount retinal dissection was performed, and labeled against Brn3a, CD90, GFAP, CD11b, Vimentin, and localization of GFP positive rBM-MSCs was used for evaluation through immunofluorescence staining and to count differentiated retinal cells by flow cytometry. From 34 male Wistar albino rats, 56 eyes were investigated. RESULTS: Flow cytometry revealed significantly increased CD90 and Brn3a positive cells in glaucoma induced and with rBM-MSC injected groups compared to control(P = 0.006 and P = 0.003 respectively), sham-operated (P = 0.007 and P < 0.001 respectively), and only rBM-MSCs injected groups (P = 0.002 and P = 0.009 respectively). Immunofluorescence microscopy revealed differentiation of GFP labeled stem cells to various retinal cells, including ganglion-like cells. rBM-MSCs were observable in ganglion cells, inner and outer nuclear retinal layers in rBM-MSCs injected eyes. CONCLUSION: Intravitreally transplanted rBM-MSCs differentiated into retinal cells, including ganglion-like cells, which successfully created a glaucoma model damaged with polystyrene microspheres. Promisingly, MSCs may have a role in neuro-protection and neuro-regeneration treatment of glaucoma in the future.

Inhalational versus Intravenous General Anesthesia for mechanical thrombectomy for stroke: A single centre retrospective study.

BACKGROUND: When general anesthesia is used for endovascular thrombectomy (EVT) for acute ischemic stroke (AIS), the choice of anesthetic agents for maintenance remains inconclusive. The different effects of intravenous anesthetic and volatiles agents on cerebral hemodynamics are known and may explain differences in outcomes of patients with cerebral pathologies exposed to the different anesthetic modalities. In this single institutional retrospective study, we assessed the impact of total intravenous (TIVA) and inhalational anesthesia on outcomes after EVT. METHODS: We conducted a retrospective analysis of all patients ≥ 18 years who underwent EVT for AIS of the anterior or posterior circulation under general anesthesia. Baseline patient characteristics, anesthetic agents, intra operative hemodynamics, stroke characteristics, time intervals and clinical outcome data were collected and analyzed. RESULTS: The study cohort consisted of 191 patients. After excluding 76 patients who were lost to follow up at 90 days, 51 patients received inhalational anesthesia and 64 patients who received TIVA were analyzed. The clinical characteristics between the groups were comparable. Multivariate logistic regression analysis of outcome measures for TIVA versus inhalational anesthesia showed significantly increased odds of good functional outcome (mRS 0-2) at 90 days (adjusted odds ratio, 3.24; 95% CI, 1.25-8.36; p = 0.015) and a non-significant trend towards decreased mortality (adjusted odds ratio, 0.73; CI, 0.15-3.6; p = 0.70). CONCLUSION: Patients who had TIVA for mechanical thrombectomy had significantly increased odds of good functional outcome at 90 days and a non-significant trend towards decrease in mortality. These findings warrant further investigation with large randomized, prospective trials.

Neuro-protective potentials of N-acetylcysteine and zinc against di(2-ethylhexyl)-phthalate-induced neuro-histopathology and dys-regulations of Dopamine and Glutamate in rat brain.

This study examined neuro-protective potentials of N-acetyl-cysteine (NAC) and Zinc on expression levels of Dopamine and Glutamate in the Cerebrum, Hypothalami and Pituitary Glands in Di(2-ethylhexyl)-phthalate (DEHP)-induced neurotoxicity in rats. Thirty-six adult male Wistar rats were randomly divided into 6 groups (n = 6). Group 1 was control. Groups 2-6 received oral administrations of 100 mg/kg NAC, 0.5 mg/kg Zinc, 750 mg/kg DEHP, DEHP + NAC doses and DEHP + Zinc doses respectively for 21 days. Brain histology (Heamatoxyline and Eosine technique), histochemical and enzyme-linked-immunosorbent assays of Dopamine and Glutamate in homogenates of Cerebrum, Hypothalami and Pituitary Glands were evaluated. Data were statistically analyzed using One-way-ANOVA with Tukey-post-hoc test at p ≤ 0.05. Histo-pathological evaluations of Cerebrum, Hypothalami and Pituitary Glands showed gross histo-alterations and neurodegenerative changes (Group 4), mild histo- and neuro-degenerative changes (Groups 5 and 6) and normal histology (Group 1). Histochemical analyses showed higher Dopamine levels in Hypothalami (Group 5) and Pituitary Glands (Groups 5 and 6), compared with Group 4. Furthermore, results showed lower Glutamate levels in Cerebrum, Hypothalami and Pituitary Glands of Groups 5 and 6, compared with Group 4. Overall, NAC and Zinc conferred neuro-protection and histo-protection against DEHP-induced neuro-toxicity, neuro-histopathology, decreased Dopamine levels and increased Glutamate levels.

Therapeutic Efficacy of Human Mesenchymal Stem Cells With Different Delivery Route and Dosages in Rat Models of Spinal Cord Injury.

Recent studies have shown that the use of mesenchymal stem/stromal cells (MSCs) may be a promising strategy for treating spinal cord injury (SCI). This study aimed to explore the effectiveness of human umbilical cord-derived MSCs (hUC-MSCs) with different administration routes and dosages on SCI rats. Following T10-spinal cord contusion in Sprague-Dawley rats (N = 60), three different dosages of hUC-MSCs were intrathecally injected into rats (SCI-ITH) after 24 h. Intravenous injection of hUC-MSCs (SCI-i.v.) and methylprednisolone reagent (SCI-PC) were used as positive controls (N = 10/group). A SCI control group without treatment and a sham operation group were injected with Multiple Electrolyte Injection solution. The locomotor function was assessed by Basso Beattie Bresnahan (BBB) rating score, magnetic resonance imaging (MRI), histopathology, and immunofluorescence. ELISA was conducted to further analyze the nerve injury and inflammation in the rat SCI model. Following SCI, BBB scores were significantly lower in the SCI groups compared with the sham operation group, but all the treated groups showed the recovery of hind-limb motor function, and rats receiving the high-dose intrathecal injection of hUC-MSCs (SCI-ITH-H) showed improved outcomes compared with rats in hUC-MSCs i.v. and positive control groups. Magnetic resonance imaging revealed significant edema and spinal cord lesion in the SCI groups, and significant recovery was observed in the medium and high-dose hUC-MSCs ITH groups. Histopathological staining showed that the necrotic area in spinal cord tissue was significantly reduced in the hUC-MSCs ITH-H group, and the immunofluorescence staining confirmed the neuroprotection effect of hUC-MSCs infused on SCI rats. The increase of inflammatory cytokines was repressed in hUC-MSCs ITH-H group. Our results confirmed that hUC-MSC administered via intrathecal injection has dose-dependent neuroprotection effect in SCI rats.

Isoalantolactone (IAL) Regulates Neuro-Inflammation and Neuronal Apoptosis to Curb Pathology of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease in which neuronal apoptosis and associated inflammation are involved in its pathogenesis. However, there is still no specific treatment that can stop PD progression. Isoalantolactone (IAL) plays a role in many inflammation-related diseases. However, its effect and mechanism in PD remain unclear. In this study, results showed that IAL administration ameliorated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD-related pathological impairment and decreased motor activity in mice. Results from in vitro mechanistic studies showed that IAL regulated apoptosis-related proteins by activating the AKT/Nrf2 pathway, thereby suppressing the apoptosis of SN4741 cells induced by N-methyl-4-phenylpyridinium Iodide (MPP+). On the other hand, IAL inhibited LPS-induced release of pro-inflammatory mediators in BV2 cells by activating the AKT/Nrf2/HO-1 pathway and inhibiting the NF-κB pathway. In addition, IAL protected SN4741 from microglial activation-mediated neurotoxicity. Taken together, these results highlight the beneficial role of IAL as a novel therapy and potential PD drug due to its pharmacological profile.

Long term therapeutic effects of icariin-loaded PLGA microspheres in an experimental model of optic nerve ischemia via modulation of CEBP-ß/G-CSF/noncanonical NF-κB axis.

An ischemic insult at optic nerve (ON) is followed by detrimental neuroinflammation that results in progressive and long-lasting retinal ganglion cell (RGC) death and vision loss. Icariin was reported to be a safe and effective natural anti-inflammatory drug. Herein, we evaluated the long-term therapeutic effects of a single intravitreal injection of poly(lactide-co-glycolide) PLGA-icariin in a rat model of anterior ischemic optic neuropathy (rAION). Treatment with PLGA microspheres of icariin preserved the visual function and RGC density for 1 month in the rAION model. In addition, ON edema and macrophage infiltration were inhibited by treating PLGA microspheres of icariin. We found that the binding complex of icariin and CCAAT enhancer binding protein beta (CEBP-ß) significantly induced endogenous granulocyte colony-stimulating factor (G-CSF) expression to activate noncanonical nuclear factor kappa B (NF-κB) signaling pathway by promoting an alternative phosphorylation reaction of IKK-ß. Activation of noncanonical NF-κB signaling pathway promoted the M2 microglia/macrophage polarization and AKT1 activation, which prevented neuroinflammation and RGC apoptosis after ON infarct. This study concluded that protective mechanism of icariin is a CEBP-ß/G-CSF axis-induced noncanonical NF-κB activation, which provides the long-term neuroprotective effects via anti-inflammatory and antiapoptotic actions after ON ischemia.

Inhalation of Atmospheric-Pressure Gas Plasma Attenuates Brain Infarction in Rats With Experimental Ischemic Stroke.

Previous studies suggest the potential efficacy of neuroprotective effects of gaseous atmospheric-pressure plasma (APP) treatment on neuronal cells. However, it remains unclear if the neuroprotective properties of the gas plasmas benefit the ischemic stroke treatment, and how to use the plasmas in the in vivo ischemic stroke models. Rats were subjected to 90 min middle cerebral artery occlusion (MCAO) to establish the ischemic stroke model and then intermittently inhaled the plasma for 2 min at 60 min MCAO. The regional cerebral blood flow (CBF) was monitored. Animal behavior scoring, magnetic resonance imaging (MRI), 2,3,5-triphenyltetrazolium chloride (TTC) staining, and hematoxylin and eosin (HE) staining were performed to evaluate the therapeutic efficacy of the gas plasma inhalation on MCAO rats. Intermittent gas plasma inhalation by rats with experimental ischemic stroke could improve neurological function, increase regional CBF, and decrease brain infarction. Further MRI tests showed that the gas plasma inhalation could limit the ischemic lesion progression, which was beneficial to improve the outcomes of the MCAO rats. Post-stroke treatment with intermittent gas plasma inhalation could reduce the ischemic lesion progression and decrease cerebral infarction volume, which might provide a new promising strategy for ischemic stroke treatment.

Phytochemistry, Ethnopharmacological Uses, Biological Activities, and Therapeutic Applications of Cassia obtusifolia L.: A Comprehensive Review.

Cassia obtusifolia L., of the Leguminosae family, is used as a diuretic, laxative, tonic, purgative, and natural remedy for treating headache, dizziness, constipation, tophobia, and lacrimation and for improving eyesight. It is commonly used in tea in Korea. Various anthraquinone derivatives make up its main chemical constituents: emodin, chrysophanol, physcion, obtusifolin, obtusin, au rantio-obtusin, chryso-obtusin, alaternin, questin, aloe-emodin, gluco-aurantio-obtusin, gluco-obtusifolin, naphthopyrone glycosides, toralactone-9-ß-gentiobioside, toralactone gentiobioside, and cassiaside. C. obtusifolia L. possesses a wide range of pharmacological properties (e.g., antidiabetic, antimicrobial, anti-inflammatory, hepatoprotective, and neuroprotective properties) and may be used to treat Alzheimer's disease, Parkinson's disease, and cancer. In addition, C. obtusifolia L. contributes to histamine release and antiplatelet aggregation. This review summarizes the botanical, phytochemical, and pharmacological features of C. obtusifolia and its therapeutic uses.

ß-hydroxybutyric acid attenuates oxidative stress and improves markers of mitochondrial function in the HT-22 hippocampal cell line.

Ketone bodies have been the topic of research for their possible therapeutic neurotropic effects in various neurological diseases such as Parkinson's disease, dementia, and seizures. However, continuing research on ketone bodies as a prophylactic agent for decreasing the risk for various neurodegenerative diseases is currently required. In this paper, hippocampal HT-22 cells were treated with ß-hydroxybutyric acid at different doses to elucidate the neurotropic effects. In addition, markers of oxidative stress, mitochondrial function, and apoptosis were investigated. As a result, the ketone body (ß-hydroxybutyric acid) showed a significant increase in hippocampal neuronal viability at a moderate dose. Results show that ß-hydroxybutyric acid exhibited antioxidant effect by decreasing prooxidant oxidative stress markers such as reactive oxygen species, nitrite content, and increasing glutathione content leading to decreased lipid peroxidation. Results show that ß-hydroxybutyric acid improved mitochondrial functions by increasing Complex-I and Complex-IV activities and showing that ß-hydroxybutyric acid significantly reduces caspase-1 and caspase-3 activities. Finally, using computational pharmacokinetics and molecular modeling software, we validated the pharmacokinetic effects and pharmacodynamic (N-Methyl-D-aspartic acid and acetylcholinesterase) interactions of ß-hydroxybutyric acid. The computational studies demonstrate that ß-hydroxybutyric acid can interact with N-Methyl-D-aspartic acid receptor and cholinesterase enzyme (the prime pharmacodynamic targets for cognitive impairment) and further validates its oral absorption, distribution into the central nervous system. Therefore, this work highlights the neuroprotective potential of ketone bodies in cognitive-related neurodegenerative diseases.

Naringenin alleviates 6-hydroxydopamine induced Parkinsonism in SHSY5Y cells and zebrafish model.

6-Hydroxydopamine (6-OHDA) is a neurotoxin that inhibits the mitochondrial complex I causing mitochondrial impairment, aetiology of Parkinson's. Naringenin is a flavanone predominantly present in citrus fruits. Due to its high antioxidant and anti-inflammatory potential, it has been widely studied against various disorders. In this study, the neuroprotective effect of naringenin was determined against 6-OHDA induced toxicity with Levodopa (l-DOPA) as the standard. Naringenin reduced 6-OHDA induced oxidative stress biomarker levels such as CAT, GSH, SOD, and ROS. Naringenin rescued 6-OHDA induced reduction of the mitochondrial membrane potential. Treatment with naringenin improved the locomotion of the 6-OHDA treated zebrafish larvae which showed stagnant swimming patterns. Naringenin was also found to downregulate the expression of some Parkinsonian genes such as casp9, lrrk2, and polg and upregulate pink1. These studies attribute to naringenin as a viable molecule to study further for its neuroprotective effects against 6-OHDA induced neurotoxicity and neurodegeneration.

Combination therapy with dipeptidyl peptidase-4 and P2X7 purinoceptor inhibitors gives rise to antiepileptic effects in rats.

OBJECTIVE(S): Although the available therapeutic agents alleviate the symptoms in patients with temporal lobe epilepsy (TLE), these antiepileptic drugs do not provide adequate control of seizures in 30-40 % of patients. This study was conducted to evaluate anti-epileptic effects of simultaneous inhibition of dipeptidyl peptidase-4 and P2 × 7 purinoceptors in Kainate treated rats. MATERIALS AND METHODS: Brilliant Blue G)BBG(, linagliptin)lin(and lin + BBG were administrated 30 min prior to induction of the intrahippocampal kainate model of epilepsy in male Wistar rats. In the case of valproic acid group, the animals intraperitoneally received valproic acid for 7 consecutive days prior to induction of the model. We carried out histological evaluations, monitoring of behavior, recording of intracranial electroencepholography (IEEG), and determination of astrogliosis and DNA fragmentation using ELISA methods. RESULTS: Our results showed that BBG and lin combination therapy had better effects on decrease in astrogliosis, DNA fragmentation and cognitive disturbances than ones whereas its effects on neuronal survival and seizure severity was similar to only BBG or lin. Likewise, the effects of lin + BBG on decrease in DNA fragmentation and cognitive disturbances were better than valproic acid group. CONCLUSION: Our findings suggest that simultaneous inhibition of dipeptidyl peptidase-4 and P2 × 7 purinoceptors might more efficiently provide protection against progression of the kainate-induced TLE in rats.

Neuroprotective effect of Allium hookeri against H2O2-induced PC12 cell cytotoxicity by reducing oxidative stress.

In this study, the anti-oxidative and neuro-protective effects of ethanolic extracts of the dried roots of Allium hookeri were investigated. Total phenolic contents and total flavonoid contents of A. hookeri extract depended on the ethanol concentrations used (50, 70 and 95%). In order to evaluate radical scavenging activity, DPPH and ABTS radical scavenging assays and ferric reducing powers were evaluated. The results showed the 95% ethanol extract of A. hookeri (95AH) had higher phenolic and flavonoid contents, and greater radical scavenging activities than 50 or 70% ethanol extracts of A. hookeri. The neuro-protective effects of 95AH were evaluated using H2O2-treated PC12 neuronal cells. Treatment of 95AH increased cell viability and superoxide dismutase and glutathione peroxidase activities, reduced lactate dehydrogenate release, reduced reactive oxygen species production, and increased Bcl-2/Bax ratio. HPLC revealed 95AH was rich in phenolics, especially catechin. These results demonstrate 95AH has substantial anti-oxidative and neuro-protective effects against H2O2-induced oxidative stress.

Improvement of cerebral ischemia/reperfusion injury by daucosterol palmitate-induced neuronal apoptosis inhibition via PI3K/Akt/mTOR signaling pathway.

Traditional Chinese medicine has growing importance in the treatment of ischemia stroke due to its abundance and low drug resistance. In this study, we aim to investigate the therapeutic potential of daucosterol palmitate against ischemia stroke, as well as its neuro-protective mechanism. The dose-response effects of daucosterol palmitate in the protection from brain damage were evaluated in a cerebral ischemia/reperfusion (I/R) rat model. The correlation of neuro-protective effects of daucosterol palmitate with apoptosis inhibition was examined and the possible signaling targets were identified. Our findings revealed that daucosterol palmitate treatment after 2 h' ischemia significantly lowered brain damage, and neuronal cell apoptosis caused by I/R injury in a dose-response mode (20, 40 and 80 mg/kg). Western blot analysis indicated that daucosterol palmitate could reverse the effects of I/R injury on protein expression of PI3K and mTOR, and phosphorylation of Akt. Contrarily, inactivation of PI3K using wortmannin dramatically antagonized the effect of daucosterol palmitate for I/R injury. With these findings, it supports the application potential of daucosterol palmitate in the treatment of ischemia stroke. Besides, the PI3K/Akt/mTOR pathway might be potential cellular targets for daucosterol palmitate.

Morphological and Functional Evaluation of Oral Citicoline Therapy in Chronic Open-Angle Glaucoma Patients: A Pilot Study With a 2-Year Follow-Up.

Aims: To study the neuroprotective effect of oral citicoline (CT) therapy in primary open-angle glaucoma (POAG). Methods: This study included one eye each of 60 POAG patients. Patients were randomly divided into two groups (A and B) of 30 participants each. Only patients of group A were administered with CT therapy. Age, sex, and disease duration were matched between groups. Despite a stable intraocular pressure (IOP), a slow disease progression-assessed by standard automated white-on-white perimetry (SAP) in the previous 3 years-occurred in all patients. All patients underwent a complete eye examination, including IOP measurement, SAP, retinal nerve fiber layer (RNFL) thickness, and ganglion cell complex (GCC) thickness measurements with optical coherence tomography (OCT), before starting CT treatment and at 6, 12, 18, and 24 months' follow-up. Parameter differences between groups were evaluated at each eye check. Results: After 18 months, mean values of SAP mean deviation (MD) of group A were significantly (p = 0.039) higher (-7.25 db) than those of group B (-8.64 db). Moreover, they appeared stable in the following visits, whereas in group B, mean MD values continued to significantly (p < 0.001) decrease (-9.28 db) over time. Mean RNFL and GCC thickness in group A were significantly (p < 0.01) higher (70.39 and 71.19 µm, respectively) than in group B (64.91 and 65.60 µm, respectively) after 12 months of CT therapy. Furthermore, they appeared to be stable over the later visits, whereas they thinned significantly (p < 0.001) over time in group B. Conclusion: These findings suggest that CT therapy seems to be effective in slowing POAG progression. Further studies on a larger population and with a longer follow-up are needed to confirm this pilot investigation.

Synthesis of sevoflurane loaded reduced graphene oxide nanoparticles system for neuroprotective effects for preconditioning against focal cerebral ischaemia.

In this study, sevoflurane (SF) loaded, Fas ligand conjugated reduced graphene oxide (rGO) system is fabricated as a therapeutic agent to target brain ischaemic region. The fluorescence investigation of mice brain denoted that the encapsulated SF in rGOs adsorbed with Fas ligand antibody could be significantly distributed to the ipsilateral side of the ischaemic brain. In addition, the immune-histochemical assay presented that the specific nanoparticles especially deposited in the ischaemic part of the tested mice model. Furthermore, SF encapsulated rGO system exhibited noticeable progress in the brain damage along with neurological deficit post ischaemia with limited dosages in contrast to regular SF. Additionally, Rhodamine labelled nanoparticles were used to find whether Fas ligand antibody has the ability to lead the SF-encapsulated nano rGO to enter the ischaemic part of brain as well as carry out neuro-protection. Overall, these experimental findings suggested that rGOs conjugated Fas ligand system could be treated as an ideal brain targeting drug for cerebral ischemia.

Opuntia dillenii: A Forgotten Plant with Promising Pharmacological Properties.

Generative and vegetative parts of the cactuses have had a long-lasting position in folk medicine and their effects could partly be confirmed in scientific experiments. Nowadays, the cactus, fruits, and cladodes are the focus of many studies because of their desirable properties. Therefore, the summarized reports of valuable properties of medicinal plants may be a good way to familiarize researches with a new source of drugs with lower side effects and higher efficacy. Opuntia dillenii, a well-known member of the Cactaceae family, is used as a medicinal plant in various countries and grows in the desert, semi-desert, tropical and sub-tropical areas. It shows diverse pharmacological activities such as: antioxidant, anti-inflammatory, anti-tumor, neuroprotective, hepatoprotective, hypotensive etc. OD fruit also possesses valuable constitutes for instance: betalains, ascorbic acid, total phenol, protein as well as essential elements which suggest the significant potential of this plant as a complementary therapy against several pathological conditions. This review describes experimental evidence about pharmacological and therapeutic potential of OD in order to give the basis of its application in the prevention and treatment of some chronic diseases. More studies on OD can help better understanding of its pharmacological mechanism of action to explain its traditional uses and to identify its potential new therapeutic applications.

Neuro-protective effect of monomethyl fumarate on ischemia reperfusion injury in rats: Role of Nrf2/HO1 pathway in peri-infarct region.

Post stroke recanalization has been associated with increased risk of oxidative stress. Stimulating endogenous antioxidant pathway by activation of nuclear factor erythroid-2-related factor-2 (Nrf2) plays a key role in neuronal defense against inflammation and oxidative stress in penumbra. Here, we explored whether monomethyl fumarate (MMF) could produce neuro-protection after ischemia/reperfusion (I/R) injury via Nrf2/HO1 activation. In male SD rats, middle cerebral artery was occluded for 90 min and confirmed using Laser Doppler flowmeter. MMF (10, 20 and 40 mg/kg) was administered in two divided doses at 30 min post ischemia and 5-10 min after reperfusion. After 24 h, effect on neurobehavioral parameters, infarct damage by TTC staining and MRI, oxidative stress and inflammatory cytokines were assessed. Expression studies of nuclear Nrf2 and cytoplasmic HO1 were performed in peri-infarct cortex and striatum; followed by dual immunofluorescence study to check the specific cell type. I/R induced neurobehavioral deficits and infarct damage were significantly (p < 0.05) attenuated by MMF (20 and 40 mg/kg). MMF, 20 mg/kg, significantly normalized I/R induced altered redox status and increased levels of TNF-α, IL-1ß in the ipsilateral cortex. MRI data showed significantly reduced infarct in cortex but not in striatum after MMF treatment. Expression of nuclear Nrf2 and cytoplasmic HO1 were significantly (p < 0.05) increased in peri-infarct cortex after treatment with MMF. Additionally, dual immunofluorescence showed increased Nrf2 expression in neurons and HO1 expression in neurons as well as astrocytes in peri-infarct cortex after MMF treatment. Our results show the neuro-protective potential of MMF probably by restricting the progression of damage from striatum to cortex through activation of Nrf2/HO1 pathway in peri-infarct cortex.

Neuro-protective effect of Levocarnitine on severe hand,foot and mouth disease after enterovirus 71 infection / 中华实用儿科临床杂志

Objective To observe the neuro-protective effect of Levocarnitine on severe hand,foot and mouth disease (HFMD) after enterovirus 71 (EV71) infection,to preliminarily explore the possible mechanism preliminarily.Methods One hundred and thirty-two children with EV71 infection and HFMD combined with serum S100 protein and neuronspecific enolase (NSE) abnormalities who were admitted to Chihlren's Hospital Affiliated to Zhengzhou University from March 2015 to July 2016 were enrolled in the study.They were divided into the routine group and the Levocarnitine group by the random number grouping method.The routine group (66 cases,including 32 males and 34 females,median age of 2 years and 3 months) was given symptomatic treatment such as antiviral therapy while the Levocarnitine group (66 cases,including 36 males and 30 females,median age of 2 years and 5 months) was treated with Levocarnitine for neuroprotection on the basis of routine group.Forty healthy children (23 males and 17 females,median age of 2 years and 6 months) who were examined at the Children's Hospital Affiliated to Zhengzhou University during the same period were selected as the healthy control group.The levels of S100,NSE,soluble apoptosis-related factors (sFas),soluble apoptosis-related factor l igands (sFasL),malondialdehyde (MDA),superoxide dismutase (SOD) in serum were compared between the healthy control group and children with HFMD.The levels of above-mentioned indexes in cerebrospinal fluid and serum,efficacy-related indicators such as duration of fever,white blood cell count on the 3rd day of treatment,time to remission of nervous system symptoms,time of disease progression and critical conversion rate were compared between 2 groups of children with HFMD.The correlation between sFas,sFasL,MDA,SOD and S100,NSEwas performed Results (1) The levels of S100 [(0.38:±:0.16) μg/Lvs.(0.06:±:0.23) μg/L],NSE [(43.70±8.80) μg/Lvs.10.10±3.60) μg/L],sFas [(6.61 ±1.86) μg/Lvs.(3.88±1.22) μg/L],sFasL [(101.40±20.7) μg/Lvs.(54.4±13.3) μg/L] and MDA[(11.98±2.54) nmol/Lvs.(4.08±1.45) nmol/L]in serum of HFMD group were significantly higher than those of the healthy control group (t =-12.245,-22.895,-8.273,-12.803,-17.960,all P ＜0.05),while the SOD level [(57.10 ± 10.40) kU/L vs.(70.3 ±14.4) kU/L] was significantly lower (t =5.457,P ＜ 0.05).(2) With the extension of treatment time for HFMD children in the two groups,S100 and NSE in cerebrospinal fluid,S100,NSE,sFas,sFasL and MDA in serum decreased,while SOD level increased.On the 3rd and 7th day after treatment,S100 (t3 =3.491,t7 =14.434),NSE (t3 =2.920,t7 =23.490) in cerebrospinal fluid,S100 (t3 =5.277,t7 =3.614),NSE (t3 =4.652,t7 =10.525),sFas (t3 =6.399,t7 =7.514),sFasL (t3 =11.155,t7 =8.804) and MDA (t3 =6.348,t7 =7.499) in serum of Levocarnitine group were significantly lower than those of routine group (all P ＜ O.05),while SOD (t3 =3.162,t7 =-3.529) was significantly higher than that of routine group (P ＜0.05).(3) The relief time of neurological symptom in levocarnitine group was significantly shorter than that in the routine group [(1.23 ± 0.65) d vs.(1.84 ± 0.47) d],and WBC on the 3rd day after treatment [(9.14 ± 2.93) × 109/L vs.(7.12 ± 2.58) × 109/L] and the progression time of the disease [(29.74 ± 7.85) h vs.(17.36 ± 8.73) h] were significantly better than the those in the routine group (t =-6.178,4.204,8.567,all P ＜ 0.05).The critical conversion rates of Levocarnitine group and the routine group were 7.58％ and 18.18％,respectively,and the difference in critical conversion rate was not statistically significant (x2 =2.316,P ＞0.05).(4)There was a positive correlation between S100 and sFas,sFasL,MDA in children with HFMD (r =0.373,0.735,0.334,P ＜ 0.05).NSE was positively correlated with sFas and sFasL (r =0.479,0.601,all P ＜0.05),while SOD and S100 were negatively correlated with NSE (r =-0.425,-0.460,all P ＜ 0.05).Conclusions Levocarnitine has good curative effect on severe HFMD in children infected by enterovirus EV71,which can effectively protect the cranial nerves.The mechanism may be related to scavenging oxygen free radicals and blocking nerve cell apoptosis.

Development of electrical stimulation treatment in retina degeneration diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retinal diseases and optic nerve injury blocked visual signal transduction from retinal neurons to visual cortex, which would cause significant influence on patients' visual function and life quality. In clinic, glaucoma, traumatic optic neuropathy, and retinitis pigmentosa and so on are accompanied with degeneration of retinal neurons or optic nerve. However, efficient neuro-protective treatment is limited. Currently, studies suggested neuro-protective and regenerative effect of electrical stimulation treatment on retinal neurons and optic nerves. In this study, we reviewed the application of electrical stimulation in ophthalmology and summarized the possible mechanism, aiming to promote the development of electrical stimulation in the study and treatment of eye diseases.