Identification and Analysis of Components in Yizhi Granule and Cynomolgus Monkey Plasma after Oral Administration by UPLC/ESI-Q-TOF MS and Their Protective Effects on PC12 Cells

Yizhi Granule (YZG) is a health food containing six traditional Chinese medicines (TCMs). It improves memory barriers in rat experiments. Here, we describe the first fast and sensitive ultraperformance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF MS) method for analyzing YZG in plasma. We used this technique for studies in cynomolgus monkey plasma. By comparing retention time, MS, and MS/MS data of reference compounds, 70 compounds were detected in YZG. Of these, 63 were identified including 60 saponins, 2 flavones, and 1 methyl ester. There were 33 saponins, 1 flavone, and 1 methyl ester in the plasma. Next, to study the therapeutic properties of YZG, the neuroprotective effect of some of the absorbed components was evaluated using PC12 cell damage caused by the Aβ25–35 model. The results showed that 9 compounds protect PC12 cells from Aβ25–35 with cell viability (%) of 111.00 ± 8.12 (G-Rb1), 102.20 ± 4.22 (G-Rb2), 100.34 ± 6.47 (G-Rd), 102.83 ± 2.10 (G-Re), 101.68 ± 7.64 (NG-Fa), 101.19 ± 7.83 (NG-R1), 102.53 ± 0.55 (NG-R2), 106.88 ± 4.95 (gypenoside A), and 103.95 ± 4.11 (gypenoside XLIX), respectively, versus the control group (87.51 ± 6.59). These results can reveal the real pharmacodynamic basis of YZG and provide a theoretical basis for subsequent studies. It can also provide some references for the research of Alzheimer’s disease.

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Isorhynchophylline Protects PC12 Cells Against Beta-Amyloid-Induced Apoptosis via PI3K/Akt Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/163057 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 19

Author(s):

Yan-Fang Xian ◽

Zhi-Xiu Lin ◽

Qing-Qiu Mao ◽

Jian-Nan Chen ◽

Zi-Ren Su ◽

...

Keyword(s):

Signaling Pathway ◽

Pc12 Cells ◽

Molecular Mechanisms ◽

Glycogen Synthase ◽

Neuroprotective Effect ◽

Protective Action ◽

Protective Effects ◽

Phosphorylated Akt ◽

Induced Apoptosis

The neurotoxicity of amyloid-β(Aβ) has been implicated as a critical cause of Alzheimer’s disease. Isorhynchophylline (IRN), an oxindole alkaloid isolated fromUncaria rhynchophylla,exerts neuroprotective effect againstAβ25–35-induced neurotoxicityin vitro. However, the exact mechanism for its neuroprotective effect is not well understood. The present study aimed to investigate the molecular mechanisms underlying the protective action of IRN againstAβ25–35-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Pretreatment with IRN significantly increased the cell viability, inhibited the release of lactate dehydrogenase and the extent of DNA fragmentation inAβ25–35-treated cells. IRN treatment was able to enhance the protein levels of phosphorylated Akt (p-Akt) and glycogen synthase kinase-3β(p-GSK-3β). Lithium chloride blockedAβ25–35-induced cellular apoptosis in a similar manner as IRN, suggesting that GSK-3βinhibition was involved in neuroprotective action of IRN. Pretreatment with LY294002 completely abolished the protective effects of IRN. Furthermore, IRN reversedAβ25–35-induced attenuation in the level of phosphorylated cyclic AMP response element binding protein (p-CREB) and the effect of IRN could be blocked by the PI3K inhibitor. These experimental findings unambiguously suggested that the protective effect of IRN againstAβ25–35-induced apoptosis in PC12 cells was associated with the enhancement of p-CREB expression via PI3K/Akt/GSK-3βsignaling pathway.

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Neuroprotective Effect of Cyperi rhizome against Corticosterone-Induced PC12 Cell Injury via Suppression of Ca2+ Overloading

Metabolites ◽

10.3390/metabo9110244 ◽

2019 ◽

Vol 9 (11) ◽

pp. 244 ◽

Cited By ~ 1

Author(s):

Jia ◽

Liu ◽

Yu ◽

Shang ◽

Zhang ◽

...

Keyword(s):

Pc12 Cells ◽

Cell Injury ◽

Cell Damage ◽

Chemical Constituents ◽

Neuroprotective Effect ◽

Vital Role ◽

Emotional Disturbances ◽

Traditional Herbal Medicine ◽

Protection Effect ◽

Independent Protein

Cyperi Rhizoma (CR) is a well-known functional food and traditional herbal medicine in Asian countries for the treatment of menstrual or emotional disturbances in women. Recent studies have shown the pharmacological effects of CR on neuronal diseases, such as Parkinson’s disease (PD) and depression. Thus, the neuroprotective effect of CR might play a vital role in exerting its effect. Here, corticosterone-induced PC12 cells were applied to screen the active fraction of CR and evaluate its neuroprotective effect. The results indicated that the fraction containing medium-polarity chemical constituents (CR-50E) displayed the best protection effect. CR-50E could increase the cell viability and reduce cell apoptosis through inhibiting oxidative stress and decreasing the lactate dehydrogenase LDH release induced by corticosterone. Further, the mechanism of action was explored by cell metabolomics. The result showed CR-50E mediated the sphingolipids metabolism of corticosterone-induced PC12 cells, which suggested inhibition of Ca2+ overloading may involve the protection of CR-50E against cell damage. The expression levels of three key proteins in calcium transport, including phospholipase A2 (PLA2), calcium/calmodulin independent protein kinase II (CaMK II), and caspase-3, confirmed the above result by Western blot. The findings suggest that CR-50E can suppress the disequilibrium of calcium homeostasis-mediated apoptosis by improving the abnormal sphingolipids metabolism as well as remedying the damage of the cell membrane.

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Resveratrol Promotes Mitochondrial Biogenesis and Protects against Seizure-Induced Neuronal Cell Damage in the Hippocampus Following Status Epilepticus by Activation of the PGC-1α Signaling Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms20040998 ◽

2019 ◽

Vol 20 (4) ◽

pp. 998 ◽

Cited By ~ 11

Author(s):

Yao-Chung Chuang ◽

Shang-Der Chen ◽

Chung-Yao Hsu ◽

Shu-Fang Chen ◽

Nai-Ching Chen ◽

...

Keyword(s):

Status Epilepticus ◽

Signaling Pathway ◽

Mitochondrial Biogenesis ◽

Neuronal Damage ◽

Cell Damage ◽

Neuroprotective Effect ◽

Neuronal Cell ◽

Protective Mechanism ◽

Protective Effects ◽

Prolonged Seizure

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is known to regulate mitochondrial biogenesis. Resveratrol is present in a variety of plants, including the skin of grapes, blueberries, raspberries, mulberries, and peanuts. It has been shown to offer protective effects against a number of cardiovascular and neurodegenerative diseases, stroke, and epilepsy. This study examined the neuroprotective effect of resveratrol on mitochondrial biogenesis in the hippocampus following experimental status epilepticus. Kainic acid was microinjected into left hippocampal CA3 in Sprague Dawley rats to induce bilateral prolonged seizure activity. PGC-1α expression and related mitochondrial biogenesis were investigated. Amounts of nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (Tfam), cytochrome c oxidase 1 (COX1), and mitochondrial DNA (mtDNA) were measured to evaluate the extent of mitochondrial biogenesis. Increased PGC-1α and mitochondrial biogenesis machinery after prolonged seizure were found in CA3. Resveratrol increased expression of PGC-1α, NRF1, and Tfam, NRF1 binding activity, COX1 level, and mtDNA amount. In addition, resveratrol reduced activated caspase-3 activity and attenuated neuronal cell damage in the hippocampus following status epilepticus. These results suggest that resveratrol plays a pivotal role in the mitochondrial biogenesis machinery that may provide a protective mechanism counteracting seizure-induced neuronal damage by activation of the PGC-1α signaling pathway.

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Neuroprotective Effect of Modified Xijiao Dihuang Decoction against Oxygen-Glucose Deprivation and Reoxygenation-Induced Injury in PC12 Cells: Involvement of TLR4-MyD88/NF-κB Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/3848595 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Xu Zhang ◽

Xiaojun Fei ◽

Weiwei Tao ◽

Jingbo Li ◽

Hao Shen ◽

...

Keyword(s):

Signaling Pathway ◽

Pc12 Cells ◽

Caspase 3 ◽

Neuroprotective Effect ◽

Glucose Deprivation ◽

Treated Group ◽

Chinese Herbs ◽

Oxygen Glucose Deprivation ◽

Control Group ◽

Stroke Treatment

Modified Xijiao Dihuang (XJDH) decoction has been shown to exert powerful neuroprotective properties in clinical ischemic stroke treatment. It consists of 4 Chinese herbs: Buffalo Horn, Paeonia suffruticosa Andrews, Rehmannia glutinosa (Gaertn.) DC, and Paeonia lactiflora Pall. In the present study, the neuroprotective effect and specific mechanisms of XJDH in protecting PC12 cells from oxygen-glucose deprivation-induced injury were investigated. It was found that OGD/R significantly decreased the cell viability and lactate dehydrogenase (LDH) activity and increased the release of IL-1β, IL-6, and TNF-α in PC12 cells, and these effects were suppressed by XJDH and one of its major active constituents, paeoniflorin. Additionally, XJDH inhibited caspase-3 activity and reduced cleaved caspase-3 level. Mechanistic studies showed that the expressions of TLR4, MyD88, TRAF6, and NF-κB p65 and phosphorylation of IκBα and p65 were significantly lower in the XJDH-treated group than in the OGD/R control group. Additionally, XJDH reversed the OGD/R-induced increases in p-JNK and p-ERK1/2 expression. These results suggest that XJDH protects PC12 cells from oxygen-glucose deprivation-induced injury, which may be associated with the inhibition of the TLR4-MyD88/NF-κB signaling pathway. As an anti-inflammation factor, XJDH might be used as a neuronal protection strategy for the ischemia injury and related diseases.

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Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy

Bioscience Reports ◽

10.1042/bsr20182332 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 1

Author(s):

Liangyan Zou ◽

Hao Yuan ◽

Qing Liu ◽

Chunmei Lu ◽

Laishuan Wang

Keyword(s):

Serum Bilirubin ◽

Neuroprotective Effect ◽

Controlled Trial ◽

Hypoxic Ischemic Encephalopathy ◽

Control Group ◽

Protective Effects ◽

Wide Range ◽

Antioxidant Function ◽

And Control ◽

Ischemic Encephalopathy

AbstractBackground: Therapeutic hypothermia (TH) is the standard therapy for hypoxic-ischemic encephalopathy (HIE) and is associated with a wide range of physiological changes. Objective: We re-evaluated the effects of HIE and TH on bilirubin measurements following HIE in a center involved in the China cooling randomized controlled trial (RCT). Methods: Serial serum bilirubin concentrations measured during the first week of life were compared among the HIE + NT (normothermia) group, HIE + TH treatment group and control group (without HIE). Survivors of HIE were followed and assessed at approximately 2 years of age, and the results were correlated with peak bilirubin levels during the first week of life. Results: One hundred and thirty-eight infants were available for analysis. Significantly lower bilirubin levels were recorded in the HIE + NT group than in the controls (P<0.05). Significant differences were not observed among the patients in the HIE + NT group (mild to severe) or between the HIE + TH group and the HIE + NT group at any time point (P>0.05). The peak serum bilirubin concentrations recorded at 96 h of age showed a good correlation with the results of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III) (P=0.02). Conclusion: Bilirubin potentially exerts a neuroprotective effect during the first week of life, and low temperature does not affect the possible antioxidant function of bilirubin during TH following HIE.

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Protective Effects and Mechanism of Hyperoside in PC12 Cells Against Oxidative Stress Injury Induced by Hydrogen Peroxide

Natural Product Communications ◽

10.1177/1934578x211015126 ◽

2021 ◽

Vol 16 (5) ◽

pp. 1934578X2110151

Author(s):

Yan Feng ◽

Dongxu Wang ◽

Qi Wang ◽

Zhifeng Li ◽

Shi-Lin Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Neurodegenerative Diseases ◽

Pc12 Cells ◽

Neuronal Damage ◽

Neuroprotective Effect ◽

Natural Antioxidants ◽

Protective Effects ◽

Stress Injury ◽

Stress Damage

As the aging phenomenon continues to increase, the incidence of neurodegenerative diseases continues to increase annually. As one of the significant contributive factors of neurodegenerative diseases, oxidative stress damage has received extensive attention in recent years. Oxidative stress plays an important role in neuronal damage through various apoptotic mechanisms related to neurodegenerative diseases. The use of natural antioxidants to combat oxidative stress may be a useful approach in delaying disease progression. In this study, we explored the neuroprotective effect of hyperoside on rat pheochromoma (PC12) cells. Specifically, the antioxidant effect and mechanism of hyperoside in hydrogen peroxide (H2O2)-induced cellular cytotoxicity were investigated. Our results showed that hyperoside could significantly increase the survival rate of rat PC12 cells when exposed to H2O2. In addition, hyperoside regulated the expression of genes and proteins in the corresponding pathways by up-regulating the phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), and light chain 3β (LC3B) pathways and down-regulating the nuclear factor-ᴋ-gene binding (NF-κB), Bcl2-associated X (Bax), cysteinyl aspartate specific proteinase 3 (Caspase 3), and P62 pathways, thereby inhibiting cell apoptosis. Therefore, hyperoside can effectively inhibit H2O2-induced oxidative stress damage by regulating inflammation, autophagy, and apoptosis-related pathways.

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Correction of ischemic optic neuropathy in rats by carbamylated darbepoetin

Research Results in Pharmacology ◽

10.3897/rrpharmacology.4.25262 ◽

2018 ◽

Vol 4 (1) ◽

pp. 43-50 ◽

Cited By ~ 2

Author(s):

Anna A. Peresypkina

Keyword(s):

Image Analysis ◽

Optic Neuropathy ◽

Neuroprotective Effect ◽

Control Group ◽

Ischemic Optic Neuropathy ◽

Image Analysis System ◽

Recombinant Erythropoietin ◽

Protective Effects ◽

Doppler Flowmetry ◽

Partial Restoration

Introduction: The protective effects of carbamylated darbepoetin on the model of ischemic optic neuropathy in rats were revealed. Objectives: To increase the effectiveness of pharmacological correction of experimental ischemic optic neuropathy in an experiment by using carbamylated darbepoetin. Methods: Measuring the microcirculation level in the retina of rats was carried out using laser Doppler flowmetry (LDF). Registration was done by the data acquisition system Biopac-systems MP-150 and AcqKnowledge 4.2 programme. For microscopy and morphometry, the prepared microslides were scanned using Mirax Desk, a computerised archiving and image analysis system. Image analysis and morphometry were carried out by Pannoramic Viewer 1.15.4. Results and discussion: In the group with correction of ischemic optic neuropathy by carbamylated darbepoetin, 300 μg/kg, the microcirculation level increases by 41.9%, p<0.05 in comparison with the control group, but also below the norm values by 20.3%, p<0.05. In the group with correction by recombinant erythropoietin, 50 IU/kg, the microcirculation rate increases by 36.7%, p<0.05 in comparison with the control group and significantly lower - by 23.3%, p<0.05 - in comparison with the group of intact animals. Qualitative and quantitative morphological indices (thickness of retinal layers) helped to reveal a neuroprotective effect of carbamylated darbepoetin to a greater extent than that of recombinant erythropoietin. Conclusion: The obtained data allow drawing a conclusion about partial restoration of blood flow and preservation of neuronal retinal structures when correcting ischemic optic neuropathy in rats with carbamylated darbepoetin to a greater extent than with recombinant erythropoietin.

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Schizandrin Protects against OGD/R-Induced Neuronal Injury by Suppressing Autophagy: Involvement of the AMPK/mTOR Pathway

Molecules ◽

10.3390/molecules24193624 ◽

2019 ◽

Vol 24 (19) ◽

pp. 3624 ◽

Cited By ~ 2

Author(s):

Guangyun Wang ◽

Tiezheng Wang ◽

Yuanyuan Zhang ◽

Fang Li ◽

Boyang Yu ◽

...

Keyword(s):

Cerebral Ischemia ◽

Pc12 Cells ◽

Cell Damage ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Mtor Pathway ◽

Protective Effects ◽

Compound C

The neuroprotective role of schizandrin (SA) in cerebral ischemia-reperfusion (I/R) was recently highlighted. However, whether SA plays a regulatory role on autophagy in cerebral I/R injury is still unclear. This study aimed to explore whether the neuroprotective mechanisms of SA were linked to its regulation of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/autophagy pathway in vivo and in vitro. The present study confirmed that SA significantly improved oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced PC12 cells injury. The results of immunoblotting and confocal microscope showed that SA decreased autophagy in OGD/R-injured PC12 cells, which was reflected by the decreased Beclin-1 and LC3-II expression, autophagy flux level, and LC3 puncta formation. In addition, the autophagy inducer rapamycin partially prevented the effects of SA on cell viability and autophagy after OGD/R, whereas the autophagy inhibitor 3-methyladenine (3-MA) exerted the opposite effect. The results of Western blotting showed that SA markedly decreased the phosphorylation of AMPK (p-AMPK), whereas the phosphor-mTOR (p-mTOR) levels increased in the presence of OGD/R insult. Furthermore, pretreatment with the AMPK inducer AICAR partially reversed the protective effects and autophagy inhibition of SA. However, AMPK inhibitor Compound C pretreatment further promoted the inhibition of SA on autophagy induction and cell damage induced by OGD/R. Taken together, these findings demonstrate that SA protects against OGD/R insult by inhibiting autophagy through the regulation of the AMPK-mTOR pathway and that SA may have therapeutic value for protecting neurons from cerebral ischemia.

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Protective Effects of Oroxylin A on Oxygen-Glucose Deprivation/Reperfusion-Induced PC12 Cells by Activating the Sonic Hedgehog Signal Pathway

Natural Product Communications ◽

10.1177/1934578x19881544 ◽

2019 ◽

Vol 14 (10) ◽

pp. 1934578X1988154

Author(s):

Yanhong Gao ◽

Rui Li ◽

Hua Sun ◽

Jianmei Li ◽

Bing He ◽

...

Keyword(s):

Pc12 Cells ◽

Oxidant Stress ◽

Glucose Deprivation ◽

Cell Counting ◽

Oxygen Glucose Deprivation ◽

Control Group ◽

Protective Effects ◽

Oroxylin A ◽

Stroke Treatment ◽

Solvent Control

Ischemic stroke is a leading cause of human death. The injury that is induced by oxygen-glucose deprivation/reperfusion in stroke remains unsolved. This study first investigated the effects of oroxylin A on oxygen-glucose deprivation/reperfusion-induced PC12 cells. This was performed by dividing the cells into a control group, an oxygen-glucose deprivation and reperfusion (OGD/R) group, a solvent control group, and experimental groups treated with different concentrations of oroxylin A. Cell viability was evaluated by Cell Counting Kit-8 assay. Relevant indicators of oxidant stress were detected by using the appropriate kits. Western blot was applied to detect the expressions of inflammatory cytokine and proteins of the signaling pathway. Oroxylin A pretreatment exerted anti-oxidative, anti-apoptotic, and anti-inflammatory effects in oxygen-glucose deprivation/reperfusion-induced PC12 cells, thus indicating it as a new avenue for stroke treatment and providing references for future studies.

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Adalimumab Ameliorates Abdominal Aorta Cross Clamping Which Induced Liver Injury in Rats

BioMed Research International ◽

10.1155/2014/907915 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Erkan Cure ◽

Medine Cumhur Cure ◽

Levent Tumkaya ◽

Yildiray Kalkan ◽

Ibrahim Aydin ◽

...

Keyword(s):

Liver Injury ◽

Abdominal Aorta ◽

Liver Tissue ◽

Cell Damage ◽

Ischemia Reperfusion ◽

Control Group ◽

Albino Rats ◽

Protective Effects ◽

Necrosis Factor Alpha ◽

Protein Levels

The aim of this study was to investigate the possible protective effects of adalimumab (ADA) on cell damage in rat liver tissue during ischemia/reperfusion (I/R) injury of infrarenal abdominal aorta. Thirty male Wistar-albino rats were divided into three groups: control, I/R, and I/R+ADA, each group containing 10 animals. Laparotomy without I/R injury was performed in the control group animals. Laparotomy in the I/R group was followed by two hours of infrarenal abdominal aortic cross ligation and then two hours of reperfusion. ADA (50 mg/kg) was administered intraperitoneally as a single dose, to the I/R+ADA group, five days before I/R. The tumor necrosis factor-alpha (TNF-α) (pg/mg protein) and nitric oxide (NO) (µmol/g protein) levels in the I/R group (430.8 ± 70.1, 8.0 ± 1.1, resp.) were significantly higher than those in the I/R+ADA group (338.0 ± 71.6,P=0.006; 6.3 ± 1.2,P=0.008) and the control group (345.5 ± 53.3,P=0.008; 6.5 ± 1.5,P=0.010, resp.). I/R causes severe histopathological injury to the liver tissue, but ADA leads to much less histopathological changes. ADA treatment significantly decreased the severity of liver I/R injury. ADA pretreatment may have protective effects on experimental liver injury.

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