Chrysanthemum coronarium L. Extract Attenuates Homocysteine-Induced Vascular Inflammation in Vascular Smooth Muscle Cells.

Hyperhomocysteinemia is a main risk factor for phenotypic modulation of vascular smooth muscle cells (VSMCs) and atherosclerosis. Phenotypic switching and proliferation of VSMCs are related to the progression of vascular inflammation. Chrysanthemum coronarium L. is a leafy vegetable with various biological functions, such as antioxidative, anti-inflammatory, and antiproliferative effects. In this study, we aimed to identify the mechanisms underlying the therapeutic and preventive effects of C. coronarium L. extract (CC) in regulating homocysteine (Hcy)-induced vascular inflammation in human aortic VSMCs. CC did not exhibit cytotoxicity and inhibited Hcy-stimulated VSMC proliferation and migration. In addition, CC promoted Hcy-induced expression of VSMC contractile phenotype proteins, including alpha-smooth muscle actin, calponin, and smooth muscle 22α. CC also decreased Hcy-induced accumulation of reactive oxygen species and expression of inflammatory markers nicotinamide adenine dinucleotide phosphate oxidase-4 and soluble epoxide hydrolase. These results showed that CC attenuates Hcy-induced inflammatory responses, highlighting its potential as a therapeutic or preventive target for Hcy-induced vascular inflammation.

Hermetia illucens Fermented with Lactobacillus plantarum KCCM12757P Alleviates Dextran Sodium Sulfate-Induced Colitis in Mice.

Inflammatory bowel disease (IBD) can severely affect humans and animals and is difficult to treat. Black soldier fly (Hermetia illucens; Hi) larvae (BSFL) are a sustainable source of protein. However, no studies exist on the antioxidant and anti-inflammatory functions of BSFL or fermented BSFL with respect to IBD. In this study, riboflavin-producing Lactobacillus plantarum KCCM12757P was isolated from a fish farm tank, and in conjunction with hot water-extracted Hi (HeHi) (termed HeHi_Lp), was used to determine optimal fermentation conditions to increase vitamin B2 concentration. This in vivo study investigated the therapeutic effects and mechanistic role of HeHi_Lp in chronic colitis-induced murine models. Histological changes, inflammatory cytokine levels, and intestinal barrier function were explored. Gut microbial communities and gene expression in the nuclear factor (NF)-κB signaling pathway were also studied. HeHi_Lp remarkably reduced the disease activity index, inflammatory cytokine (inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor α, interleukin (IL-6 and IL-1ß) levels, and increased body weight and colon length. HeHi_Lp administration significantly raised zonula occludens 1, occludin and claudin 1 and improved the composition of the gut microbiota and beneficial intestinal bacteria. These results suggest that HeHi_Lp can be used as a dietary supplement in pet food to alleviate colitis.

Effect of Menaquinone-4 on Receptor Activator of Nuclear Factor κB Ligand-Induced Osteoclast Differentiation and Ovariectomy-Induced Bone Loss.

Osteoporosis is a progressive metabolic disease characterized by decreased bone mineral density and increased fracture risk. Previous studies have shown that higher intake of vitamin K (VK) correlates with a reduced risk of osteoporosis. However, the effect of menaquinone-4 (MK-4), a specific form of VK, still remains obscure. Therefore, in this study, we investigated the effects of MK-4 on osteoclast differentiation by differentiating RAW 264.7 cells into osteoclasts with the help of receptor activator of nuclear factor-kappa B ligand (RANKL), assessed the mRNA expression of osteoclast-specific genes, and studied the effects of MK-4 in vivo in ovariectomized mice, a postmenopausal osteoporosis murine model. MK-4 inhibited osteoclast differentiation, decreased the mRNA expression of nuclear factor of activated T cells c1 (NFATc1), osteoclast-associated receptor (OSCAR), and cathepsin K (CTSK), and inhibited bone loss in ovariectomized mice. The findings strongly suggest that MK-4 is a therapeutic alternative for postmenopausal osteoporosis.

Hyperthermic intraperitoneal chemotherapy for epithelial ovarian cancer: A meta-analysis.

BACKGROUND: The value of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of cytoreductive surgery (CRS) for epithelial ovarian cancer (EOC) is controversial and its use remains experimental in most national and international guidelines. We wished to systematically evaluate all available evidence. METHODS: A comprehensive review of data from MEDLINE, EMBASE, and Cochrane Library databases was conducted from the first report on HIPEC in EOC till April 3, 2022. Progression-free survival (PFS) and overall survival (OS) were compared between the HIPEC and control groups. This meta-analysis was registered with PROSPERO (CRD42021265810). RESULTS: Fifteen studies (10 case-control studies and 5 randomized controlled trials [RCTs]) were included in the present meta-analysis. Based on the time interval between the last systemic chemotherapy exposure and timing of CRS +/- HIPEC, all studies and patients' cohorts we classified into recent (<6 months; n = 9 studies/patients cohorts) and non-recent (≥6 months, n = 8 studies/patients cohorts) chemotherapy exposure groups. In the recent chemotherapy exposure group, HIPEC was associated with improvement of both PFS (HR, 0.585; 95% CI, 0.422-0.811) and OS (HR, 0.519; 95% CI, 0.346-0.777). On the contrary, in the non-recent chemotherapy exposure group, HIPEC failed to significantly affect PFS (HR, 1.037; 95% CI, 0.684-1.571) or OS (HR, 0.932; 95% CI, 0.607-1.430). Consistent results were observed in subsequent sensitivity analyses. CONCLUSION: Our present meta-analysis demonstrates that the value of HIPEC at CRS for EOC appears to depend on the timing of the last systemic chemotherapy exposure. Future trials are awaited to define the role of HIPEC in EOC.

Combined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy.

IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.

Status of Four Trace Elements in Elderly Patients with Online Hemodiafiltration.

BACKGROUND: Essential trace elements play key roles in multiple biological systems, and hemodialysis patients are at risk for deficiency of essential trace elements. The aim of the study was to assess the essential element status in end stage renal disease patients undergoing online hemodiafiltration (online HDF) in outpatient dialysis clinic. METHODS: A total of 28 Korean patients with regular online HDF were included. Blood samples were collected before and after one HDF session, and serum concentrations of zinc, copper, selenium, and manganese were simulta-neously measured by inductively coupled plasma mass spectrometry. RESULTS: Selenium, zinc, copper deficiencies were observed in 71.4%, 35.8%, and 21.4%, compared with the reference range. No patients revealed manganese deficiency. After the HDF, the post-HDF level significantly increased in all trace elements, compared with the pre-HDF (11.2% for selenium, 10.7% for copper, and 6.6% for zinc). However, 50% patients were still deficient for selenium at the post-HDF. CONCLUSIONS: Our data suggest that the patients undergoing online HDF are at an increased risk of trace element deficiency, especially for selenium.

Development of a One-item Screening Question to Assess Spiritual Well-Being for Advanced Cancer Inpatients in Korea.

CONTEXT: Spiritual well-being (SWB) is significant for patients with life-limiting illnesses. Thus, shortened versions of questions would be helpful in approaching SWB. OBJECTIVES: Our goal was to develop a one-item screening question to assess the SWB of advanced cancer inpatients. METHODS: This was a cross-sectional, multicenter study involving adult advanced cancer inpatients from seven palliative care units in South Korea. The candidate one-item questions were three questions scored using numeric rating scales from 0 to 10: feeling at peace (Are you at peace?), self-rated spirituality (Do you think of yourself as a spiritual person?), and self-rated religiosity (Do you think of yourself as a religious person?). The Functional Assessment of Chronic Illness Therapy-Spirituality 12 (FACIT-Sp-12) comprised of two subscales Meaning/Peace and Faith was used to assess SWB. Pearson's correlation test was conducted to determine the relationship between the three questions, the total FACIT-Sp-12 score, and its subscales. RESULTS: A total of 202 patients were enrolled. A strong correlation was observed between self-rated spirituality (r = 0.732 and 0.790; P < 0.001 and < 0.001 respectively) and religiosity (r = 0.708 and 0.758; P < 0.001 and < 0.001 respectively) with the total FACIT-Sp-12 scores and faith subscale scores. Feeling at peace showed a moderate correlation with the total of FACIT-Sp-12 scores (r = 0.505, P < 0.01). All three questions had a moderate correlation with the meaning/peace subscale. CONCLUSION: Self-rated spirituality and religiosity showed better convergence validity than feeling at peace. Therefore, we recommend self-rated spirituality or religiosity as a one-item question for screening SWB in inpatients with advanced cancer.

Glycyrrhetinic Acid-Modified Silicon Phthalocyanine for Liver Cancer-Targeted Photodynamic Therapy.

To supplement shortcomings of existing treatments and enhance the therapeutic effect for liver cancer, a novel photosensitizer is designed using silicon phthalocyanine (SiPC) and a unique targeting moiety, glycyrrhetinic acid (GA). The SiPC is modified with a hydrophilic polymer and finally bound with GA. The solubility, fluorescence, singlet oxygen generation, and UV-vis absorbance are analyzed, and receptor-dependent intracellular influx is estimated in various cell lines. Using flow cytometry and confocal microscopy, intracellular fluorescence was detected in liver cancer because of GA receptor overexpression. To prove in vitro photodynamic therapeutic effects, the sample treated cells are irradiated and viability of liver cancer cells decreases in proportion to laser power. Then, it is confirmed that GA-modified SiPC effectively accumulated in liver cancer of HepG2 tumor-bearing mouse. Additionally, the PDT-combined therapeutic effect of GA-modified SiPC is observed in the tumor model and shown to have a tumor growth inhibition effect (60.36 times higher than the control group) and supported by histological analyses. These results demonstrate that the newly modified SiPC can be applied to liver cancer-specific treatment with high therapeutic efficacy. Consequently, novel SiPC has the potential to alter conventional liver cancer-targeted therapy and chemotherapy in clinical use.

Dietary Exposure to Acrylamide and Associated Health Risks for the Korean Population.

The aim of the study was to estimate the dietary exposure to acrylamide (AA) from the consumption of various processed food and to assess the associated health risks in different age groups in Korea. Potato crisps and French fries presented the highest mean levels of AA (546 and 372 µg/kg, respectively) followed by coffee (353 µg/kg) and tea products (245 µg/kg). The mean AA dietary exposure values for toddlers (≤2 years), children (3-6 years), children (7-12 years), adolescents (13-19 years), adults (20-64 years), and seniors (≥65 years) were estimated to be 0.15, 0.13, 0.06, 0.06, 0.08, and 0.06 µg/kg body weight (BW)/day, respectively. Based on the benchmark dose lower confidence limit (BMDL10) of 0.18 and 0.31 mg/kg BW/day, the calculated mean and 95th percentile values for the margin of exposure were below 10,000 for the all age groups suggesting possible health concern for Koreans. Biscuits, crisps, and coffee were the primary foods contributing to dietary AA exposure among these in the Korean populations. In children, considering the health risk of AA dietary exposure, especially from biscuits and crisps, there is a need to further control and modify dietary habits to ensure lower AA exposure.

Leaf extracts from Dendropanax morbifera Léveille mitigate mercury-induced reduction of spatial memory, as well as cell proliferation, and neuroblast differentiation in rat dentate gyrus.

BACKGROUND: The brain is susceptible to methylmercury toxicity, which causes irreversible damage to neurons and glia and the leaf extract Dendropanax morbifera Léveille (DML) has various biological functions in the nervous system. In this study, we examined the effects of DML on mercury-induced proliferating cells and differentiated neuroblasts. METHODS: Dimethylmercury (5 µg/kg) and galantamine (5 mg/kg) was administered intraperitoneally and/or DML (100 mg/kg) was orally to 7-week-old rats every day for 36 days. One hour after the treatment, novel object recognition test was examined. In addition, spatial probe tests were conducted on the 6th day after 5 days of continuous training in the Morris swim maze. Thereafter, the rats were euthanized for immunohistochemical staining analysis with Ki67 and doublecortin and measurement for acetylcholinesterase (AChE) activity. RESULTS: Dimethylmercury-treated rats showed reduced discrimination index in novel object recognition test and took longer to find the platform than did control group. Compared with dimethylmercury treatment alone, supplementation with DML or galatamine significantly ameliorated the reduction of discrimination index and reduced the time spent to find the platform. In addition, the number of platform crossings was lower in the dimethylmercury-treated group than in controls, while the administration of DML or galantamine significantly increased the number of crossings than did dimethylmercury treatment alone. Proliferating cells and differentiated neuroblasts, assessed by Ki67 and doublecortin immunohistochemical staining was significantly decreased in the dimethylmercury treated group versus controls. Supplementation with DML or galantamine significantly increased the number of proliferating cells and differentiated neuroblasts in the dentate gyrus. In addition, treatment with dimethylmercury significantly increased AChE activity in hippocampal homogenates, while treatment with dimethylmercury+DML or dimethylmercury+galantamine significantly ameliorated this increase. CONCLUSIONS: These results suggest that DML may be a functional food that improves dimethylmercury-induced memory impairment and ameliorates dimethylmercury-induced reduction in proliferating cells and differentiated neuroblasts, and demonstrates corresponding activation of AChE activity in the dentate gyrus.

Metabolomics Analysis of the Lipid-Regulating Effect of Allium hookeri in a Hamster Model of High-Fat Diet-Induced Hyperlipidemia by UPLC/ESI-Q-TOF Mass Spectrometry.

Hyperlipidemia is a risk factor for atherosclerotic cardiovascular disease and is a major public health concern. Allium hookeri (AH) is an Allium species containing high levels of bioactive organosulfur compounds such as methiin and cycloalliin. AH exerts hypolipidemic effects in animals fed a high-fat diet. However, there exists little information on the mechanisms underlying these effects. To address this issue, we used a metabolomic approach based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry to identify factors mediating the lipid-lowering effects of AH. Principal component and partial least-squares discriminant analyses of serum metabolome profiles revealed 25 metabolites as potential biomarkers for the effects of AH on lipid levels. These compounds were predominantly phospholipids, including phosphatidylcholines (PCs), lysoPCs, and lysophosphatidylethanolamines. Glycerophospholipid metabolism was identified as a significantly enriched pathway. These results provide mechanistic insight into the antihyperlipidemic effects of AH and evidence for its efficacy as a therapeutic agent.

Comparative studies of bioactive organosulphur compounds and antioxidant activities in garlic (Allium sativum L.), elephant garlic (Allium ampeloprasum L.) and onion (Allium cepa L.).

We evaluated organosulphur compounds in Allium vegetables, including garlic, elephant garlic and onion, using high-performance liquid chromatography. Among organosulphur compounds, elephant garlic had considerable γ-glutamyl peptides, and garlic had the highest alliin content. Onion had low level of organosulphur compounds than did elephant garlic and garlic. In addition, antioxidant capacities were evaluated by oxygen radical absorbance capacity (ORAC) values and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging assay. The results showed that garlic had the highest antioxidant capacity, followed by elephant garlic and onion. Furthermore, a positive correlation was observed between antioxidant activities and organosulphur compounds (R > 0.77). Therefore, our results indicate that there was a close relationship between antioxidant capacity and organosulphur compounds in Allium vegetables.

Is spirituality related to survival in advanced cancer inpatients in Korea?

OBJECTIVE: Spirituality is what gives people meaning and purpose in life, and it has been recognized as a critical factor in patients' well-being, particularly at the ends of their lives. Studies have demonstrated relationships between spirituality and patient-reported outcomes such as quality of life and mental health. Although a number of studies have suggested that spiritual belief can be associated with mortality, the results are inconsistent. We aimed to determine whether spirituality was related to survival in advanced cancer inpatients in Korea. METHOD: For this multicenter study, we recruited adult advanced cancer inpatients who had been admitted to seven palliative care units with estimated survival of <3 months. We measured spirituality at admission using the Korean version of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-sp), which comprises two subscales: meaning/peace and faith. We calculated a Kaplan-Meier curve for spirituality, dichotomized at the predefined cutoffs and medians for the total scale and each of the two subscales, and performed univariate regression with a Cox proportional hazard model.ResultWe enrolled a total of 204 adults (mean age: 64.5 ± 13.0; 48.5% female) in the study. The most common primary cancer diagnoses were lung (21.6%), colorectal (18.6%), and liver/biliary tract (13.0%). Median survival was 19.5 days (95% confidence interval [CI95%]: 23.5, 30.6). Total FACIT-sp score was not related to survival time (hazard ratio [HR] = 0.981, CI95% = 0.957, 1.007), and neither were the scores for its two subscales, meaning/peace (HR = 0.969, CI95% = 0.932, 1.008) and faith (HR = 0.981, CI95% = 0.938, 1.026).Significance of resultsSpirituality was not related to survival in advanced cancer inpatients in Korea. Plausible mechanisms merit further investigation.

Supraventricular tachyarrhythmias in patients with a persistent left superior vena cava.

Aims: A persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly. This venous anomaly can impact the evaluation and treatment of supraventricular tachyarrhythmia (SVA). The aim of this study was to assess the proportion and characteristics of PLSVC in adult SVA patients. Methods and results: From July 2002 to July 2012, clinical and procedural data from databases of 10 cardiac electrophysiology laboratories in the Yeungnam region of the Republic of Korea were reviewed. Of 6662 adult SVA patients who underwent an EP study or catheter ablation of SVA during the 10-year study period, 18 patients had PLSVC (mean age 47.6 ± 14.8 years, 10 men). The proportion of PLSVC in adult SVA patients was 0.27% (18/6662). SVA type and procedural outcomes of radiofrequency (RF) catheter ablation in these patients were investigated and the results were as follows: successful slow pathway modification in six of seven patients with atrioventricular nodal reentrant tachycardia (AVNRT), successful ablation of accessory pathway in three of four patients with atrioventricular reentrant tachycardia, and successful ablation of atrial tachycardia (cavotricuspid isthmus-dependent in two, septal macroreentry in one, focal from the PLSVC in one) in three of four patients. In one patient with junctional tachycardia, catheter ablation failed. In two patients with atrial fibrillation, catheter ablation was successful. Conclusion: Among adult SVA patients who underwent an EP study or RF catheter ablation during the 10-year study period, 0.27% had PLSVC. The most common type of SVA was AVNRT. The success rate of catheter ablation was 82% in SVA patients with PLSVC. There were no procedure-related complications.

Essential oils from two Allium species exert effects on cell proliferation and neuroblast differentiation in the mouse dentate gyrus by modulating brain-derived neurotrophic factor and acetylcholinesterase.

BACKGROUND: In the present study, we investigated the effects of oil products from two Allium species: Allium sativum (garlic) and Allium hookeri (Chinese chives) on cell proliferation and neuroblast differentiation in the mouse dentate gyrus. METHODS: Using corn oil as a vehicle, the essential oil from garlic (10 ml/kg), or Chinese chives (10 ml/kg) was administered orally to 9-week-old mice once a day for 3 weeks. One hour following the last treatment, a novel object recognition test was conducted and the animals were killed 2 h after the test. RESULTS: In comparison to the vehicle-treated group, garlic essential oil (GO) treatment resulted in significantly increased exploration time and discrimination index during the novel object recognition test, while Chinese chives essential oil (CO) reduced the exploration time and discrimination index in the same test. In addition, the number of Ki67-immunoreactive proliferating cells and doublecortin-immunoreactive neuroblasts significantly increased in the dentate gyrus of GO-treated animals. However, administration of CO significantly decreased cell proliferation and neuroblast differentiation. Administration of GO significantly increased brain-derived neurotrophic factor (BDNF) levels and decreased acetylcholinesterase (AChE) activity in the hippocampal homogenates. In contrast, administration of CO decreased BDNF protein levels and had no significant effect on AChE activity, compared to that in the vehicle-treated group. CONCLUSIONS: These results suggest that GO significantly improves novel object recognition as well as increases cell proliferation and neuroblast differentiation, by modulating hippocampal BDNF protein levels and AChE activity, while CO impairs novel object recognition and decreases cell proliferation and neuroblast differentiation, by reducing BDNF protein levels in the hippocampus.

UPLC/ESI-MS/MS analysis of compositional changes for organosulfur compounds in garlic (Allium sativum L.) during fermentation.

In this study, we used liquid chromatography coupled to ion trap mass spectrometry (MS) for the quantification of 11 organosulfur compounds and analysis of their compositional changes in garlic during fermentation using 3 different microbe strains. The calibration curves of all 11 analytes exhibited good linearity (R⩾0.995), and the mean recoveries measured at three concentrations were greater than 81.63% with relative standard deviations of less than 12.79%. Investigation of the compositional changes revealed that the γ-glutamyl peptides content in fermented blanched garlic reduced, whereas the content of the compounds in biosynthesis of S-allyl-l-cysteines from γ-glutamyl peptides increased significantly. Our results also indicated that starter cultures can be used selectively in the production of fermented garlic to increase the amounts of the desired organosulfur compounds.

Valerenic Acid Protects Against Physical and Psychological Stress by Reducing the Turnover of Serotonin and Norepinephrine in Mouse Hippocampus-Amygdala Region.

In a previous study, we demonstrated that a Valeriana officinalis extract could attenuate increases in serum corticosterone levels in a mouse model of physical and psychological stress. In addition, our results showed that the extract could modulate serotonin (5-HT) and norepinephrine (NE) turnover in the hippocampus and amygdala region. In this study, we intended to investigate the effects of valerenic acid (VA), the main component of V. officinalis extract, on corticosterone levels in serum in normal mice and monoamine turnover in hippocampus-amygdala homogenates in a mouse model of physical and psychological stress. To determine the minimum dose of VA for antianxiety effect, eight-week-old ICR mice were orally administered VA (0.2, 0.5, and 1.0 mg/kg/0.3 mL) once daily for 3 weeks to probe for immobility time and serum corticosterone levels. At a VA dose of 0.5 and 1.0 mg/kg, animals showed a decrease in the duration of immobility time and serum corticosterone levels. To confirm the antianxiety effect of VA, eight-week-old ICR mice received VA at a dose of 0.5 mg/kg, orally, once daily for 3 weeks, before being subjected to physical or psychological stress for 3 days, in a specially designed communication box, followed by estimation of levels of monoamines and their metabolites in the hippocampus-amygdala region. In conclusion, VA administration at 0.5 mg/kg can mitigate the physical and psychological stress response by decreasing the turnover of 5-HT to 5-hydroxyindoleacetic acid and NE to 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in the hippocampus and amygdala.

Valeriana officinalis Extracts Ameliorate Neuronal Damage by Suppressing Lipid Peroxidation in the Gerbil Hippocampus Following Transient Cerebral Ischemia.

As a medicinal plant, the roots of Valeriana officinalis have been used as a sedative and tranquilizer. In the present study, we evaluated the neuroprotective effects of valerian root extracts (VE) on the hippocampal CA1 region of gerbils after 5 min of transient cerebral ischemia. Gerbils were administered VE orally once a day for 3 weeks, subjected to ischemia/reperfusion injury, and continued on VE for 3 weeks. The administration of 100 mg/kg VE (VE100 group) significantly reduced the ischemia-induced spontaneous motor hyperactivity 1 day after ischemia/reperfusion. Four days after ischemia/reperfusion, animals treated with VE showed abundant cresyl violet-positive neurons in the hippocampal CA1 region when compared to the vehicle or 25 mg/kg VE-treated groups. In addition, the VE treatment markedly decreased microglial activation in the hippocampal CA1 region 4 days after ischemia. Compared to the other groups, the VE100 group showed the lowest level of lipid peroxidation during the first 24 h after ischemia/reperfusion. In summary, the findings in this study suggest that pretreatment with VE has protective effects against ischemic injury in the hippocampal pyramidal neurons by decreasing microglial activation and lipid peroxidation.

Neuroprotective effects of Z-ajoene, an organosulfur compound derived from oil-macerated garlic, in the gerbil hippocampal CA1 region after transient forebrain ischemia.

The neuroprotective effects of two isomers (Z- and E-) of ajoene, a major compound in oil-macerated garlic products, against ischemic damage were investigated in the gerbil hippocampus. Vehicle (corn oil), Z- or E-ajoenes (25 mg/kg) was orally administered 30 min prior to the induction of transient forebrain ischemia by occlusion of the common carotid arteries for 5 min. One day after ischemia/reperfusion (I/R), I/R-induced hyperactivity significantly reduced in the E- and Z-ajoene-treated groups, compared to that in the vehicle-treated group 5 days after I/R, the number of cresyl violet-positive neurons in the E- and Z-ajoene-treated groups increased, compared to that in the vehicle-treated group. Reactive gliosis in the CA1 region of E- and Z-ajoene-treated groups reduced, compared to that in the vehicle-treated group. These neuroprotective effects were more prominent in animals treated with Z-ajoene, than in those treated with E-ajoene. In addition, Z-ajoene significantly decreased lipid peroxidation, as indicated by 4-hydroxy-2-nonenal levels in hippocampal homogenates, compared to that observed in the vehicle-treated group at a range of time points after I/R. These results suggested that Z-ajoene protected against I/R-induced delayed neuronal death and gliosis by reducing lipid peroxidation in the gerbil hippocampal CA1 region.

Effects of curcumin (Curcuma longa) on learning and spatial memory as well as cell proliferation and neuroblast differentiation in adult and aged mice by upregulating brain-derived neurotrophic factor and CREB signaling.

Aging is a progressive process, and it may lead to the initiation of neurological diseases. In this study, we investigated the effects of wild Indian Curcuma longa using a Morris water maze paradigm on learning and spatial memory in adult and D-galactose-induced aged mice. In addition, the effects on cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin (DCX) respectively. The aging model in mice was induced through the subcutaneous administration of D-galactose (100 mg/kg) for 10 weeks. C. longa (300 mg/kg) or its vehicle (physiological saline) was administered orally to adult and D-galactose-treated mice for the last three weeks before sacrifice. The administration of C. longa significantly shortened the escape latency in both adult and D-galactose-induced aged mice and significantly ameliorated D-galactose-induced reduction of cell proliferation and neuroblast differentiation in the subgranular zone of hippocampal dentate gyrus. In addition, the administration of C. longa significantly increased the levels of phosphorylated CREB and brain-derived neurotrophic factor in the subgranular zone of dentate gyrus. These results indicate that C. longa mitigates D-galactose-induced cognitive impairment, associated with decreased cell proliferation and neuroblast differentiation, by activating CREB signaling in the hippocampal dentate gyrus.