Neuroprotective Effect Of Berberine Research Articles

Investigation of Antioxidant and Anti-inflammatory Properties of Berberine Nanomicelles: In vitro and In vivo Studies.

In the present study, neuroprotective effects of berberine (BBR) and berberine nanomicelle (BBR-NM) against lipopolysaccharides (LPS)-induced stress oxidative were investigated, and compared by evaluating their antioxidant and anti-inflammatory activities in PC12 cells, and rat brains. A fast, green, and simple synthesis method was used to prepare BBR-NMs. The prepared BBR-NMs were then characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In vitro experiments were carried out on the LPS-treated PC12 cell lines to investigate the anti-cytotoxic and antioxidant properties of BBR-NM and BBR. The results showed that BBR-NMs with a diameter of ~100 nm had higher protective effects against ROS production and cytotoxicity induced by LPS in PC12 cells in comparison with free BBR. Moreover, in vivo experiments indicated that the activity levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), increased in the brain of LPS-treated rats administrated with BBR-NM at the optimum dose of 100 mg.kg-1. BBR-NM administration also resulted in decreased concentration of lipid peroxidation (MDA) and pro-inflammatory cytokines, such as Serum interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Overall, BBR-NM demonstrated higher neuroprotective effects than free BBR, making it a promising treatment for improving many diseases caused by oxidative stress and inflammation.

Oxyberberine protects middle cerebral artery occlusion triggered cerebral injury through TLR4/NLRP3 pathway in rats

Cerebral ischemia is a life-threatening health concern that leads to severe neurological complications and fatalities worldwide. Although timely intervention with clot-removing agents curtails serious post-stroke neurological dysfunctions, no effective neuroprotective intervention is available for addressing post-recanalization neuroinflammation. Herein, for the first time we studied the effect of oxyberberine (OBB), a derivative of berberine, on transient middle cerebral artery occlusion (MCAO)-generated neurological consequences in Sprague-Dawley rats. The MCAO-operated rats exhibited significant somatosensory and sensorimotor dysfunctions in adhesive removal, foot fault, paw whisker, and rotarod assays at 1 and 3 days post-surgery. These MCAO-generated neurological deficits were prevented in OBB-treated (50 and 100 mg/kg) rats, and also coincided with a smaller infarct area (in 2,3,5-triphenyl tetrazolium chloride staining) and decreased neuronal death (in cresyl violet staining) in the ipsilateral hemisphere of these animals. The immunostaining of neuronal nuclear protein (NeuN) and glial-fibrillary acidic protein (GFAP) also echoes the neuroprotective nature of OBB. The increased expression of neuroinflammatory and blood-brain barrier tight junction proteins like toll-like receptor 4 (TLR4), TRAF-6, nuclear factor kappa B (NF-κB), pNF-κB, nNOS, ASC, and IKBα in the ipsilateral part of MCAO-operated rats were restored to normal following OBB treatment. We also observed the decline in plasma levels/mRNA transcription of TNF-α, IL-1β, NLRP3, IL-6, and matrix metalloproteinase-9 and increased expression of occludin and claudin in OBB-treated rats. These outcomes imply that OBB may prevent the MCAO-induced neurological consequences and neuroinflammation by interfering with TLR4 and NLRP3 signaling in rats.

Neuroprotective effect of berberine by amelioration of behavioural, biochemical and histological anomalies on valproate induced autistic features in experimental animals

ObjectiveThe goal of the current investigation was to establish the therapeutic prospective of berberine (BBR), the golden alkaloid of traditional Chinese medicine (TCM) for the treatment of valproic acid (VPA)-induced oxidative stress and neuronal damage in a postnatal model of autism, which is characterized by behavioural, biochemical, and histopathological changes. MethodsPups of the Wistar albino rat were divided into five categories of six at the age of 13 days: the vehicle-treated group (1 mg/mL normal saline), the VPA group (VPA 400 mg/kg, s.c.), the BBR per se, low (50 mg/kg, p.o.) and high dose (100 mg/kg, p.o.), marked as BBR I and BBR II. On postnatal day (PND) 14, everyone received 400 mg/kg (s.c.) of valproic acid (VPA), with the exception of the group that had received vehicle therapy. Berberine was given every day between PND 14 and 40. All the groups (II-V) getting routine therapy, were assessed for various neuro-behavioural indicators. Towards the conclusion of the study, animals were euthanized on PND 41 for antioxidant, inflammatory and histopathological computations. Results: Autism was effectively caused with a single dosage of 400 mg/kg s.c. of VPA. Treatment with berberine considerably improved neuro-behavioural activity, biochemical and inflammatory alterations, along with histological abnormalities in comparison to animals of autistic group. The results were more prominent at larger doses of berberine, providing proof that the deficiencies in autistic behaviour caused by valproic acid may be reversed. ConclusionBerberine exhibited neuro-protective benefits, perhaps as a result of its antioxidant and anti-inflammatory action, thus may be beneficial in the treatment of autism spectrum disorder (ASD). Future research is needed to fully understand berberine's mode of action and potential contribution to human autism spectrum disorders.

The efficacy and mechanism of berberine in improving aging-related cognitive dysfunction: A study based on network pharmacology.

To analyze the effects and mechanisms of berberine in the treatment of aging-related cognitive dysfunction based on network pharmacology methods, molecular docking techniques, and animal experiments. A mouse model of cognitive dysfunction was constructed by subcutaneous injection of D-galactose (D-gal) for 10 weeks, and the neuroprotective effects of berberine on aging-related cognitive dysfunction mice were evaluated by the Morris water maze (MWM) and immunofluorescence staining. The targets of berberine were obtained by SwissTargetPrediction, GeneCards, and PharmMapper. Putative targets of cognitive dysfunction were obtained by GeneCards, TTD, and DrugBank database. The STRING database and Cytoscape software were applied for protein-protein interaction (PPI) analysis and further screening of core targets. The DAVID database was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analysis to clarify the biological processes and pathways involved in the intersection targets, and AutoDockTools was adopted for molecular docking verification of core targets. Finally, the core genes were validated using real-time quantitative PCR. The MWM results showed that treatment with berberine significantly improved spatial learning and memory in mice with cognitive decline induced by D-gal. Immunofluorescence staining indicated that berberine modified the levels of aging-related markers in the brain. A total of 386 berberine putative targets associated with cognitive dysfunction were identified based on the public database. The core targets of berberine for improving cognitive function, include Mapk1, Src, Ctnnb1, Akt1, Pik3ca, Tp53, Jun, and Hsp90aa1. GO enrichment and KEGG pathway enrichment analyses indicated that the mechanism of berberine in the treatment of aging-related cognitive dysfunction is attributed to pathways such as PI3K-AKT and MAPK pathways. In vivo experiments further confirmed that Akt1, Ctnnb1, Tp53, and Jun were involved in the neuroprotective actions of berberine. This study reveals the multi-target and multi-pathway effects of berberine on regulating aging-related cognitive dysfunction, which provides preclinical evidence and may promote new drug development in mitigating cognitive dysfunction.

A Review on the Neuroprotective Effect of Berberine against Chemotherapy- induced Cognitive Impairment.

Chemobrain is one of the major side effects of chemotherapy; despite increased research, the mechanisms underlying chemotherapy-induced cognitive changes remain unknown. Several possibly important candidate mechanisms have been identified and will be studied further in the future. Chemobrain is characterized by memory loss, cognitive impairment, difficulty in language, concentration, acceleration, and learning. The major characteristic of chemobrain is oxidative stress, mitochondrial dysfunction, immune dysregulation, hormonal alteration, white matter abnormalities, and DNA damage. Berberine (BBR) is an isoquinoline alkaloid extracted from various berberine species. BBR is a small chemical that easily passes the blood-brain barrier (BBB), making it useful for treating neurodegenerative diseases. Many studies on the pharmacology of BBR have been reported in the past. Furthermore, several clinical and experimental research indicates that BBR has a variety of pharmacological effects. So, in this review, we explore the pathogenesis of chemobrain and the neuroprotective potential of BBR against chemobrain. We also introduced the therapeutic role of BBR in various neurodegenerative and neurological diseases such as Alzheimer's, Parkinson's disease, mental depression, schizophrenia, anxiety, and also some stroke.

Novel mechanistic insight on the neuroprotective effect of berberine: The role of PPARδ for antioxidant action

Cerebral ischemic stroke ranks the second leading cause of death and the third leading cause of disability in lifetime all around the world, urgently necessitating effective therapeutic interventions. Reactive oxygen species (ROS) have been implicated in stroke pathogenesis and peroxisome proliferator-activated receptors (PPARs) are prominent targets for ROS management. Although recent research has shown antioxidant effect of berberine (BBR), little is known regarding its effect upon ROS-PPARs signaling in stroke. The aim of this study is to explore whether BBR could target on ROS-PPARs pathway to ameliorate middle cerebral artery occlusion (MCAO)-induced stroke. Herein, we report that BBR is able to scavenge ROS in oxidation-damaged C17.2 neural stem cells and stroked mice. PPARδ, rather than PPARα or PPARγ, is involved in the anti-ROS effect of BBR, as evidenced by the siRNA transfection and specific antagonist treatment data. Further, we have found BBR could upregulate NF-E2 related factor-1/2 (NRF1/2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) following a PPARδ-dependent manner. Mechanistic study has revealed that BBR acts as a potent ligand (Kd = 290 ± 92 nM) to activate PPARδ and initiates the transcriptional regulation functions, thus promoting the expression of PPARδ, NRF1, NRF2 and NQO1. Collectively, our results indicate that BBR confers neuroprotective effects by activating PPARδ to scavenge ROS, providing a novel mechanistic insight for the antioxidant action of BBR.

Berberine Ameliorates Subarachnoid Hemorrhage Injury via Induction of Sirtuin 1 and Inhibiting HMGB1/Nf-κB Pathway.

Excessive cerebral inflammation plays a key role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Berberine, an isoquinoline alkaloid isolated from Chinese herb Coptis chinensis, possesses anti-inflammatory, and neuroprotective effects. Here we evaluated the beneficial effects of berberine against SAH-induced inflammatory response and the subsequent brain injury. Our data showed that berberine treatment significantly inhibited microglia activation and proinflammatory cytokines release. Concomitant with suppressed cerebral inflammation, berberine mitigated the subsequent brain injury as demonstrated by improved neurological behavior, reduced brain edema, and decreased neural apoptosis. Moreover, berberine significantly inhibited high mobile group box 1 (HMGB1)/nuclear factor-κB (Nf-κB)-dependent pathway and enhanced sirtuin 1 (SIRT1) expression after SAH. Treatment with ex527, a selective SIRT1 inhibitor, reversed berberine-induced SIRT1 activation and inhibitory effects on HMGB1/Nf-κB activation. In addition, ex527 pretreatment abated the anti-inflammatory and neuroprotective effects of berberine on SAH. Taken together, these findings suggest that berberine provides beneficial effects against SAH-triggered cerebral inflammation by inhibiting HMGB1/Nf-κB pathway, which may be modulated by SIRT1 activation.

Protein kinase C is involved in the neuroprotective effect of berberine against intrastriatal injection of quinolinic acid-induced biochemical alteration in mice.

Protein kinase C (PKC) shows a neuronal protection effect in neurodegenerative diseases. In this study, we test whether berberine has a positive effect on the activity of PKC in quinolinic acid (QA)‐induced neuronal cell death. We used intrastriatal injections of QA mice model to test the effect of berberine on motor and cognitive deficits, and the PKC signalling pathway. Treatment with 50 mg/kg b.w of berberine for 2 weeks significantly prevented QA‐induced motor and cognitive impairment and related pathologic changes in the brain. QA inhibited the phosphorylation of PKC and its downstream molecules, GSK‐3β, ERK and CREB, enhanced the glutamate level and release of neuroinflammatory cytokines; these effects were attenuated by berberine. We used in vivo infusion of Go6983, a PKC inhibitor to disturb PKC activity in mice brain, and found that the effect of berberine to reverse motor and cognitive deficits was significantly reduced. Moreover, inhibition of PKC also blocked the anti‐excitotoxicity effect of berberine, which is induced by glutamate in PC12 cells and BV2 cells, as well as anti‐neuroinflammatory effect in LPS‐stimulated BV2 cells. Above all, berberine showed neuroprotective effect against QA‐induced acute neurotoxicity by activating PKC and its downstream molecules.

Neuroprotective effects of berberine in animal models of Alzheimer\u2019s disease: a systematic review of pre-clinical studies

BackgroundBerberine is an isoquinoline alkaloid extracted from various Berberis species which is widely used in East Asia for a wide range of symptoms. Recently, neuroprotective effects of berberine in Alzheimer’s disease (AD) animal models are being extensively reported. So far, no clinical trial has been carried out on the neuroprotective effects of berberine. However, a review of the experimental data is needed before choosing berberine as a candidate drug for clinical experiments. We conducted a systematic review on AD rodent models to analyze the drug effects with minimal selection bias.MethodsFive online literature databases were searched to find publications reporting studies of the effect of berberine treatment on animal models of AD. Up to March 2018, 15 papers were identified to describe the efficacy of berberine.ResultsThe included 15 articles met our inclusion criteria with different quality ranging from 3 to 5. We analyzed data extracted from full texts with regard to pharmacological effects and potential anti-Alzheimer’s properties. Our analysis revealed that in multiple memory defects animal models, berberine showed significant memory-improving activities with multiple mechanisms, such as anti-inflammation, anti-oxidative stress, cholinesterase (ChE) inhibition and anti-amyloid effects.ConclusionAD is likely to be a complex disease driven by multiple factors. Yet, many therapeutic strategies based on lowering β-amyloid have failed in clinical trials. This suggest that the threapy should not base on a single cause of Alzheimer’s disease but rather a number of different pathways that lead to the disease. Overall we think that berberine can be a promising multipotent agent to combat Alzheimer’s disease.

Neuroprotective effects of berberine on recognition memory impairment, oxidative stress, and damage to the purinergic system in rats submitted to intracerebroventricular injection of streptozotocin.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. The present study investigated the effects of 50 and 100mg/kg berberine (BRB) on recognition memory, oxidative stress, and purinergic neurotransmission, in a model of sporadic dementia of the Alzheimer's type induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats. Rats were submitted to ICV-STZ 3mg/kg or saline, and 3days later, were started on a treatment of BRB or saline for 21days. The results demonstrated that BRB was effective in protecting against memory impairment, increased reactive oxygen species, and the subsequent increase in protein and lipid oxidation in the cerebral cortex and hippocampus, as well as δ-aminolevulinate dehydratase inhibition in the cerebral cortex. Moreover, the decrease in total thiols, and the reduced glutathione and glutathione S-transferase activity in the cerebral cortex and hippocampus of ICV-STZ rats, was prevented by BRB treatment. Besides an antioxidant effect, BRB treatment was capable of preventing decreases in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase (EC-5'-Nt), and adenosine deaminase (ADA) activities in synaptosomes of the cerebral cortex and hippocampus. Thus, our data suggest that BRB exerts a neuroprotective effect on recognition memory, as well as on oxidative stress and oxidative stress-related damage, such as dysfunction of the purinergic system. This suggests that BRB may act as a promising multipotent agent for the treatment of AD.

The neuroprotective effects of Berberine against amyloid β-protein-induced apoptosis in primary cultured hippocampal neurons via mitochondria-related caspase pathway.

Neuronal cell apoptosis is an important pathological change in Alzheimer's disease (AD). Berberine, an isoquinoline alkaloid isolated and extracted from Coptidis and rhizome and Cortex phellodendri, has a wide range of pharmacological effects. In this study, we investigated the neuroprotective effects of Berberine against neuronal insults induced by Aβ25-35 in primary cultured hippocampal neurons. Primary neuron cells have been isolated from hippocampus of C57BL/6 newborn mice. We investigated effect of Berberine against neuronal insults induced by Aβ25-35 in primary cultured hippocampal neurons. TdT-mediated dUTP nick-end labeling, MTT, Propidium iodide, MMP, Caspase activity measurement, Western blot. These neurons explosure to the β25-35 protein resulted in a loss in cell viability and a surge in apoptosis. However, the presence of Berberine significantly reversed the effects induced by Aβ25-35. Through decreasing viability and caspase activity in neurons, the pretreatment with Berberine attenuated the cytotoxic effect of the Aβ25-35. Furthermore, it's found that expression of cytochrome C, as well as the restoration of Bcl-2/Bax and Bcl-xl/Bax ratio in the presence of Berberine, led to a decline in the apoptotic rate. The neuroprotective effects of Berberine against Aβ25-35-induced neuronal apoptosis, suggesting that this may be a promising therapeutics against AD.

Neuroprotective effect of berberine is mediated by MAPK signaling pathway in experimental diabetic neuropathy in rats

The mechanisms leading to diabetic neuropathy are complex. As an active component in several traditional Chinese medicines, berberine has a beneficial effect in the treatment of diabetes with hyperlipidemia. This study evaluated the protective effects of berberine on diabetic neuropathy induced by streptozotocin and a high-carbohydrate/high-fat diet in rats. Diabetic neuropathy was induced in rats by intraperitoneal injection of 35mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Two weeks after diabetes induction, rats were treated with berberine (100mg/kg) and rosiglitazone (4mg/kg) for 24 weeks. Rats were studied using evoked potentials, the Morris water maze, transmission electron microscopy, real-time PCR, and Western blotting. Blood glucose, glycated hemoglobin, lipid profile, body weight, evoked potentials, and memory were altered in diabetic rats, as was the hippocampal expression of neuritin mRNA, p38 mitogen-activated protein kinase mRNA, c-Jun N-terminal kinase (JNK) mRNA, extracellular signal-regulated kinase mRNA and the phospho-proteins of p38, JNK, and extracellular signal-regulated kinase. In diabetic rats, berberine decreased body weight and the blood levels of glucose, glycated hemoglobin, triglyceride, and total cholesterol, improved memory and affected evoked potential by decreasing latency. Berberine decreased the mRNA expression of neuritin, p38, and JNK and the protein expression of neuritin, p-p38, and p-JNK. Slight micropathological changes were observed in the hippocampus of berberine-treated diabetic rats. These findings suggest that berberine has a beneficial effect against diabetic neuropathy by improving micropathology and increasing neuritin expression via the mitogen-activated protein kinase signaling pathway.

Possible role of P-glycoprotein in the neuroprotective mechanism of berberine in intracerebroventricular streptozotocin-induced cognitive dysfunction

The therapeutic potential of berberine has been well documented in various neurological problems. However, the neurological mechanism of berberine remains untapped in the light of its P-glycoprotein (P-gp)-mediated gut efflux properties responsible for reduced bioavailability. Verapamil, a well known L-type calcium channel blocker, has additional inhibitory activity against P-gp efflux pump. Thus, there is a strong scientific rationale to explore the interaction of berberine with verapamil as a possible neuroprotective strategy. The present study was designed to evaluate the effect of berberine, verapamil, and their combination on behavioral alterations, oxidative stress, mitochondrial dysfunction, neuroinflammation, and histopathological modifications in intracerebroventricular streptozocin (ICV-STZ)-induced sporadic dementia of Alzheimer's type in rats. Single bilateral ICV-STZ (3mg/kg) administration was used as an experimental model of sporadic dementia of Alzheimer's type. Berberine (25, 50, and 100mg/kg, oral gavage) or verapamil (2.5 and 5mg/kg, intraperitoneally) were used as treatment drugs, and memantine (5mg/kg, intraperitoneally) was used as a standard. Berberine and verapamil significantly attenuated behavioral, biochemical, cellular, and histological alterations, suggesting their neuroprotective potential. Further, treatment of berberine (25 and 50mg/kg) with verapamil (2.5 and 5.0mg/kg) combinations respectively significantly potentiated their neuroprotective effect which was significant as compared to their effect per se in ICV-STZ-treated animals. The augmentative outcome of verapamil on the neuroprotective effect of berberine can be speculated due to the inhibition of P-gp efflux mechanism and the prevention of calcium homeostasis alteration. Additionally, anti-inflammatory and antioxidant effects of both berberine and verapamil could also contribute in their protective effect.

The neuroprotective effect of berberine in mercury-induced neurotoxicity in rats.

The central nervous system is one of the most vulnerable organs affected by mercury toxicity. Both acute and chronic exposure to mercury is also known to cause a variety of neurological or psychiatric disorders. Here, the neuroprotective effect of berberine (BN; 100mg/kg bwt) on mercuric chloride (HgCl2; 0.4mg/kg bwt) induced neurotoxicity and oxidative stress was examined in rats. Adult male albino Wistar rats were injected with HgCl2 for 7days. HgCl2 treatment induced oxidative stress by increasing lipid peroxidation (LPO) and nitrite/nitrate (nitric oxide; NO) production along with a concomitant decrease in glutathione (GSH) and various antioxidant enzymes, namely superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Pre-treatment of rats with BN inhibited LPO and NO production, whereas it increased GSH content. Activities of antioxidant enzymes were also restored concomitantly when compared to the control rats after BN administration. Berberine also caused decrease in TNF-α level and caspase-3 activity which was higher with HgCl2. Furthermore, treatment with BN inhibited apoptosis, as indicated by the reduction of Bax/Bcl-2 ratio in brain tissue. These data indicated that BN augments antioxidant defense with anti-inflammatory and anti-apoptotic activities against HgCl2-induced neurotoxicity and provides evidence that it has a therapeutic potential as neuroprotective agent.

Mercury-induced neurotoxicity and neuroprotective effects of berberine.

Mercury-induced neurotoxicity and neuroprotective effects of berberine.

Inhibition of Retinoblastoma mRNA Degradation through Poly (A) Involved in the Neuroprotective Effect of Berberine against Cerebral Ischemia

Berberine is one kind of isoquinoline alkaloid with anti-apoptotic effects on the neurons suffering ischemia. To address the explanation for these activities, the berberine-induced cell cycle arrest during neurons suffering ischemia/reperfusion had been studied in the present study. According to the in vitro neurons with oxygen-glucose deprivation and in vivo ICR mice with cerebral ischemia/reperfusion, it was found that berberine could protect the mRNA of retinoblastoma (Rb) from degradation through its function on the poly(A) tail. The prolonged half-life of retinoblastoma 1 (gene of Rb, RB1) mRNA level secures the protein level of retinoblastoma, which facilitates cell cycle arrest of neurons in the process of ischemia/reperfusion and subsequently avoids cells entering in the apoptotic process. The poly(A) tail of RB1 mRNA, as a newly identified target of berberine, could help people focus on the interaction between berberine and mRNA to further understand the biological activities and functions of berberine.

Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway.

PurposeBerberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the hippocampus using gerbils.MethodsGerbils received berberine orally once a day for 14 consecutive days, starting one day after surgery. In this study, a step-down avoidance task was used to assess short-term memory. Furthermore, we employed the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate DNA fragmentation, immunohistochemistry to investigate glial fibriallary acidic protein, CD11b, and caspase-3, and western blot to assess PI3K, Akt, Bax, Bcl-2, and cytochrome c.ResultsOur results revealed that berberine treatment alleviated ischemia-induced short-term memory impairment. Treatment with berbeine also attenuated ischemia-induced apoptosis and inhibited reactive astrogliosis and microglia activation. Furthermore, berberine enhanced phospho-PI3K and phospho-Akt expression in the hippocampus of ischemic gerbils.ConclusionsBerberine exerted a neuroprotective effect against ischemic insult by inhibiting neuronal apoptosis via activation of the PI3K/Akt signaling pathway. The antiapoptotic effect of berberine was achieved through inhibition of reactive astrogliosis and microglia activation. Berberine may therefore serve as a therapeutic agent for stroke-induced neurourological problems.

Neuroprotective effects of berberine on stroke models in vitro and in vivo

Berberine is an alkaloid derived from herb medicine Coptidis Rhizom. Although there are increasing evidences that berberine exhibits neuroprotective effects against ischemic brain damage, little is known about the mechanism. In this study, we investigated the effect of berberine on ischemic injury in a middle cerebral artery occlusion (MCAO) model. We found that berberine improved neurological outcome and reduced ischemia/reperfusion (I/R)-induced cerebral infarction 48 h after MCAO. The protective effect of berberine was confirmed in in vitro study. Berberine protected PC12 cells against oxygen-glucose deprivation (OGD)-induced injury. The results showed that berberine inhibited reactive oxygen species (ROS) generation, and subsequent release of pro-apoptotic factor cytochrome c and apoptosis-inducing factors (AIFs) evoked by OGD. Findings of this study suggest that berberine protects against ischemic brain injury by decreasing the intracellular ROS level and subsequently inhibiting mitochondrial apoptotic pathway.

Neuroprotective effects of berberine in neurodegeneration model rats induced by ibotenic acid

Berberine, an isoquinoline alkaloid found in Coptidis Rhizoma (goldenthread) extract, has multiple pharmacological effects such as anti‐inflammatory, antimicrobial and anti‐ischemic effects. In the present study, we examined the effects of berberine on neuronal survival and differentiation in a hippocampal precursor cell line and in the memory deficient rat model. Berberine increased in a dose dependent manner the survival of hippocampal precursor cells as well as differentiated cells. In addition, berberine promoted neuronal differentiation of hippocampal precursor cells. In the memory deficient rat model induced by stereotaxic injection of ibotenic acid into entorhinal cortex (Ibo model), hippocampal cells were increased about 2.7 fold in the pyramidal layer of CA1 region and about 2 fold in the dentate gyrus by administration of berberine after 2 weeks of ibotenic acid injection. Furthermore, neuronal cells immunoreactive to calbindin were increased in the hippocampus and entorhinal cortex area by administration of berberine. Taken together, these results suggest that berberine has neuroprotective effect in the Ibo model rat brain by promoting the neuronal survival and differentiation.

Psychosocial aspects of neoplastic disease: II. Affective and cognitive effects of chemotherapy in cancer patients.

A battery of cognitive and affective tests administered to 50 consecutively admitted medical oncology patients revealed cognitive impairment to be a common occurrence in the absence of affective disorders or other psychopathology. Chemotherapy was the major variable associated with cognitive impairment in these patients. These findings suggest that the consultant psychiatrist should be aware of chemotherapy as a possible source of behavioral change and emotional distress in cancer patients.