Rutin protects against neuronal damage in vitro and ameliorates doxorubicin-induced memory deficits in vivo in Wistar rats

Three lactic acid bacterial strains,Lactobacillus plantarum, HK006, and HK109, andPediococcus pentosaceusPP31 exhibit probiotic potential as antiallergy agents, both in vitro and in vivo. However, the safety of these new strains requires evaluation when isolated from infant faeces or pickled cabbage. Multiple strains (HK006, HK109, and PP31) were subject to a bacterial reverse mutation assay and a short-term oral toxicity study. The powder product exhibited mutagenic potential inSalmonellaTyphimurium strains TA98 and TA1535 (with or without metabolic activation). In the short-term oral toxicity study, rats received a normal dosage of 390 mg/kg/d (approximately9×109 CFU/kg/d) or a high dosage of 1950 mg/kg/d (approximately4.5×1010 CFU/kg/d) for 28 d. No adverse effects were observed regarding the general condition, behaviour, growth, feed and water consumption, haematology, clinical chemistry indices, organ weights, or histopathologic analysis of the rats. These studies have demonstrated that the consumption of multiple bacterial strains is not associated with any signs of mutagenicity ofS.Typhimurium or toxicity in Wistar rats, even after consuming large quantities of bacteria.

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Dangguijakyak-San Protects against 1-Methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-Induced Neuronal Damage via Anti-Inflammatory Action

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/976270 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Deok-Sang Hwang ◽

Hyo Geun Kim ◽

Jun-Bock Jang ◽

Myung Sook Oh

Keyword(s):

Neuronal Damage ◽

Cell Damage ◽

Substantia Nigra Pars Compacta ◽

Inflammatory Factors ◽

Dopaminergic Cell ◽

Therapeutic Implications ◽

Anti Inflammatory ◽

Inflammatory Action

Dangguijakyak-san (DJS), a famous traditional Korean multiherbal medicine, has been used to treat gynecological and neuro-associated disease. Recent studies demonstrated that DJS has multiple bioactivities including neuroprotection. In the present study, we were to investigate the effect of DJS and its mechanism in anin vitroandin vivomodel of Parkinson’s disease (PD). In primary mesencephalic culture system, DJS attenuated the dopaminergic cell damage induced by 1-methyl-4-phenylpyridine toxicity, and it inhibited production of inflammatory factors such as tumor necrosis factorα(TNF-α), nitric oxide (NO), and activation of microglial cells. Then, we confirmed the effect of DJS in a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the pole test, DJS at 50 mg/kg/day for 5 days showed increase of motor activity showing shortened time to turn and locomotor activity compared with the MPTP only treated mice. In addition, DJS significantly protected nigrostriatal dopaminergic neuron from MPTP stress. Moreover, DJS showed inhibition of gliosis in the substantia nigra pars compacta. These results have therapeutic implications for DJS in the treatment of PD via anti-inflammatory effects.

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Neuroprotection by Brazilian Green Propolis againstIn vitroandIn vivoIschemic Neuronal Damage

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/neh078 ◽

2005 ◽

Vol 2 (2) ◽

pp. 201-207 ◽

Cited By ~ 56

Author(s):

Masamitsu Shimazawa ◽

Satomi Chikamatsu ◽

Nobutaka Morimoto ◽

Satoshi Mishima ◽

Hiroichi Nagai ◽

...

Keyword(s):

Oxidative Stress ◽

Cerebral Ischemia ◽

Neuronal Damage ◽

Focal Cerebral Ischemia ◽

Brain Infarction ◽

Folk Medicine ◽

Neuroprotective Function ◽

Brazilian Green Propolis

We examined whether Brazilian green propolis, a widely used folk medicine, has a neuroprotective functionin vitroand/orin vivo.In vitro, propolis significantly inhibited neurotoxicity induced in neuronally differentiated PC12 cell cultures by either 24 h hydrogen peroxide (H2O2) exposure or 48 h serum deprivation. Regarding the possible underlying mechanism, propolis protected against oxidative stress (lipid peroxidation) in mouse forebrain homogenates and scavenged free radicals [induced by diphenyl-p-picrylhydrazyl (DPPH). In micein vivo, propolis [30 or 100 mg/kg; intraperitoneally administered four times (at 2 days, 1 day and 60 min before, and at 4 h after induction of focal cerebral ischemia by permanent middle cerebral artery occlusion)] reduced brain infarction at 24 h after the occlusion. Thus, a propolis-induced inhibition of oxidative stress may be partly responsible for its neuroprotective function againstin vitrocell death andin vivofocal cerebral ischemia.

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MiR-30a-5p Downregulation Induces Neuronal Autophagy by Activating AMPK After 2856MHz Microwave Radiation

10.21203/rs.3.rs-1063942/v1 ◽

2021 ◽

Author(s):

Yanhui Hao ◽

Wenchao Li ◽

Hui Wang ◽

Jing Zhang ◽

Haoyu Wang ◽

...

Keyword(s):

Microwave Radiation ◽

Hippocampal Neurons ◽

Target Genes ◽

Neuronal Damage ◽

Luciferase Reporter ◽

Potential Health ◽

Downstream Target ◽

Neuronal Autophagy

Abstract Background With the development of science and technology, microwaves are being widely used. More and more attention has been paid to the potential health hazards of microwave exposure. The regulation of miR-30a-5p (miR-30a) on autophagy is involved in the pathophysiological process of many diseases. Our previous study found that 30 mW/cm2 microwave radiation could reduce miR-30a expression and activate neuronal autophagy in rat hippocampus. However, the roles played by miR-30a in microwave-induced neuronal autophagy and related mechanisms remain largely unexplored. Results In the present study, we established neuronal damage models by exposing rat hippocampal neurons and rat adrenal pheochromocytoma (PC12) cell-derived neuron-like cells to 30 mW/cm2 microwave, which resulted in miR-30a downregulation and autophagy activation in vivo and in vitro. Bioinformatics analysis was conducted, and Beclin1, Prkaa2, Irs1, Pik3r2, Rras2, Ddit4, Gabarapl2 and autophagy-related gene 12 (Atg12) were identified as potential downstream target genes of miR-30a involved in regulating autophagy. Based on our previous findings that microwave radiation can cause a neuronal energy metabolism disorder, Prkaa2, encoding adenosine 5’-monophosphate-activated protein kinase α2 (AMPKα2, an important catalytic subunit of energy sensor AMPK), was selected for further analysis. Dual-luciferase reporter assay results showed that Prkaa2 is a downstream target gene of miR-30a. Microwave radiation increased the expression and phosphorylation (Thr172) of AMPKα both in vivo and in vitro. Moreover, the transduction of cells with miR-30a mimics suppressed AMPKα2 expression, inhibited AMPKα (Thr172) phosphorylation and reduced autophagy flux in neuron-like cells. Importantly, miR-30a mimics abolished microwave-activated autophagy and inhibited microwave-induced AMPKα (Thr172) phosphorylation. Conclusions AMPKα2 was a newly founded downstream gene of miR-30a involved in autophagy regulation, and miR-30a downregulation after microwave radiation could promote neuronal autophagy by increasing AMPKα2 expression and activating AMPK signaling.

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Upregulation of PKR pathway mediates glucolipotoxicity induced diabetic cardiomyopathy in vivo in wistar rats and in vitro in cultured cardiomyocytes

Biochemical Pharmacology ◽

10.1016/j.bcp.2020.113948 ◽

2020 ◽

Vol 177 ◽

pp. 113948

Author(s):

Sureshbabu Mangali ◽

Audesh Bhat ◽

Kirtikumar Jadhav ◽

Jaspreet Kalra ◽

Dharmarajan Sriram ◽

...

Keyword(s):

Diabetic Cardiomyopathy ◽

Wistar Rats ◽

Cultured Cardiomyocytes

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Delving into the Antiurolithiatic Potential of Tribulus terrestris Extract Through –In Vivo Efficacy and Preclinical Safety Investigations in Wistar Rats

Scientific Reports ◽

10.1038/s41598-019-52398-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Jyoti Kaushik ◽

Simran Tandon ◽

Rishi Bhardwaj ◽

Tanzeer Kaur ◽

Surinder Kumar Singla ◽

...

Keyword(s):

Body Weight ◽

Aqueous Extract ◽

Kidney Stones ◽

Wistar Rats ◽

Lethal Dose ◽

Tribulus Terrestris ◽

Oral Toxicity ◽

Preclinical Safety

Abstract Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.

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Brain Factor-7® improves learning and memory deficits and attenuates ischemic brain damage by reduction of ROS generation in stroke in vivo and in vitro

Laboratory Animal Research ◽

10.1186/s42826-020-00057-x ◽

2020 ◽

Vol 36 (1) ◽

Author(s):

Yoohun Noh ◽

Ji Hyeon Ahn ◽

Ji-Won Lee ◽

Junkee Hong ◽

Tae-Kyeong Lee ◽

...

Keyword(s):

Learning And Memory ◽

Brain Damage ◽

Memory Deficits ◽

Ros Generation ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Learning And Memory Deficits ◽

Brain Factor

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Effect of bFGF on neuronal damage induced by sequential treatment of amyloid β and excitatory amino acid in vitro and in vivo

European Journal of Pharmacology ◽

10.1016/j.ejphar.2012.09.020 ◽

2012 ◽

Vol 695 (1-3) ◽

pp. 76-82 ◽

Cited By ~ 10

Author(s):

Takafumi Noshita ◽

Norihito Murayama ◽

Tetsushi Oka ◽

Ryoko Ogino ◽

Shizuo Nakamura ◽

...

Keyword(s):

Amino Acid ◽

Excitatory Amino Acid ◽

Neuronal Damage ◽

Amyloid Β ◽

Sequential Treatment

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Amazon rainforest rodents (Proechimys) are resistant to post-stroke epilepsy

Scientific Reports ◽

10.1038/s41598-021-96235-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nancy N. Ortiz-Villatoro ◽

Selvin Z. Reyes-Garcia ◽

Leandro Freitas ◽

Laís D. Rodrigues ◽

Luiz E. C. Santos ◽

...

Keyword(s):

Wistar Rats ◽

Laboratory Research ◽

Post Injury ◽

Post Stroke ◽

Brain Responses ◽

Conventional Animal ◽

Acquired Epilepsy ◽

Brain Insults

AbstractThere are no clinical interventions to prevent post-injury epilepsy, a common and devastating outcome after brain insults. Epileptogenic events that run from brain injury to epilepsy are poorly understood. Previous studies in our laboratory suggested Proechimys, an exotic Amazonian rodent, as resistant to acquired epilepsy development in post-status epilepticus models. The present comparative study was conducted to assess (1) stroke-related brain responses 24-h and 30 days after cortical photothrombosis and (2) post-stroke epilepsy between Proechimys rodents and Wistar rats, a traditional animal used for laboratory research. Proechimys group showed smaller volume of ischemic infarction and lesser glial activation than Wistar group. In contrast to Wistar rats, post-stroke decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators and growth factors were found in Proechimys. Electrophysiological signaling changes assessed by cortical spreading depression, in vitro and in vivo, showed that Wistar’s brain is most severely affected by stroke. Chronic electrocorticographic recordings showed that injury did not lead to epilepsy in Proechimys whereas 88% of the Wistar rats developed post-stroke epilepsy. Science gains insights from comparative studies on diverse species. Proechimys rodents proved to be a useful animal model to study antiepileptogenic mechanisms after brain insults and complement conventional animal models.

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DHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid Haemorrhage

Journal of Neuroinflammation ◽

10.1186/s12974-019-1641-y ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 7

Author(s):

Tao Tao ◽

Guang-Jie Liu ◽

Xuan Shi ◽

Yan Zhou ◽

Yue Lu ◽

...

Keyword(s):

Subarachnoid Haemorrhage ◽

Microglial Activation ◽

Neuronal Damage ◽

Neuroprotective Effect ◽

Early Brain Injury ◽

Protective Effects ◽

In Vivo Models ◽

The Brain

Abstract Background Microglia are resident immune cells in the central nervous system and central to the innate immune system. Excessive activation of microglia after subarachnoid haemorrhage (SAH) contributes greatly to early brain injury, which is responsible for poor outcomes. Dehydroepiandrosterone (DHEA), a steroid hormone enriched in the brain, has recently been found to regulate microglial activation. The purpose of this study was to address the role of DHEA in SAH. Methods We used in vivo models of endovascular perforation and in vitro models of haemoglobin exposure to illustrate the effects of DHEA on microglia in SAH. Results In experimental SAH mice, exogenous DHEA administration increased DHEA levels in the brain and modulated microglial activation. Ameliorated neuronal damage and improved neurological outcomes were also observed in the SAH mice pretreated with DHEA, suggesting neuronal protective effects of DHEA. In cultured microglia, DHEA elevated the mRNA and protein levels of Jumonji d3 (JMJD3, histone 3 demethylase) after haemoglobin exposure, downregulated the H3K27me3 level, and inhibited the transcription of proinflammatory genes. The devastating proinflammatory microglia-mediated effects on primary neurons were also attenuated by DHEA; however, specific inhibition of JMJD3 abolished the protective effects of DHEA. We next verified that DHEA-induced JMJD3 expression, at least in part, through the tropomyosin-related kinase A (TrkA)/Akt signalling pathway. Conclusions DHEA has a neuroprotective effect after SAH. Moreover, DHEA increases microglial JMJD3 expression to regulate proinflammatory/anti-inflammatory microglial activation after haemoglobin exposure, thereby suppressing inflammation.

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