Platycodon grandiflorum root extract inhibits Aß deposition by breaking the vicious circle linking oxidative stress and neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by irreversible cognitive impairment. A deleterious feedback loop between oxidative stress and neuroinflammation in early AD exacerbates AD-related pathology. Platycodon grandiflorum root extract (PGE) has antioxidant and anti-inflammatory effects in several organs. However, the mechanisms underlying the effects of PGE in the brain remain unclear, particularly regarding its impact on oxidative/inflammatory damage and Aß deposition. Thus, we aim to identify the mechanism through which PGE inhibits Aß deposition and oxidative stress in the brain by conducting biochemical and histological analyses. First, to explore the antioxidant mechanism of PGE in the brain, we induced oxidative stress in mice injected with scopolamine and investigated the effect of PGE on cognitive decline and oxidative damage. We also assessed the effect of PGE on reactive oxygen species (ROS) generation and the expressions of antioxidant enzymes and neurotrophic factor in H2O2- and Aß-treated HT22 hippocampal cells. Next, we investigated whether PGE, which showed antioxidant effects, could reduce Aß deposition by mitigating neuroinflammation, especially microglial phagocytosis. We directly verified the effect of PGE on microglial phagocytosis, microglial activation markers, and pro-inflammatory cytokines in Aß-treated BV2 microglial cells. Moreover, we examined the effect of PGE on neuroinflammation, inducing microglial responses in Aß-overexpressing 5XFAD transgenic mice. PGE exerts antioxidant effects in the brain, enhances microglial phagocytosis of Aß, and inhibits neuroinflammation and Aß deposition, ultimately preventing neuronal cell death in AD. Taken together, our findings indicate that the therapeutic potential of PGE in AD is mediated by its targeting of multiple pathological processes.

Heat Treatment Enhances the Neuroprotective Effects of Crude Ginseng Saponin by Increasing Minor Ginsenosides.

Ginsenoside is the primary active substance of ginseng and has many pharmacological effects, such as anti-cancer, immune, regulating sugar and lipid metabolism, and antioxidant effects. It also protects the nervous and cardiovascular systems. This study analyzes the effects of thermal processing on the bioactivities of crude ginseng saponin. Heat treatment increased the contents of minor ginsenosides in crude saponins, such as Rg3, and heat-treated crude ginseng saponin (HGS) had better neuroprotective effects than non-treated crude saponin (NGS). HGS reduced glutamate-induced apoptosis and reactive oxygen species generation in pheochromocytoma 12 (PC12) cells, significantly more than NGS. HGS protected PC12 cells against glutamate-induced oxidative stress by upregulating Nrf2-mediated antioxidant signaling and downregulating MAPK-mediated apoptotic signaling. HGS has the potential for the prevention and treatment of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease.

Extract of Aster koraiensis Nakai Leaf Ameliorates Memory Dysfunction via Anti-inflammatory Action.

Aster koraiensis Nakai (AK) leaf reportedly ameliorates health problems, such as diabetes. However, the effects of AK on cognitive dysfunction or memory impairment remain unclear. This study investigated whether AK leaf extract could attenuate cognitive impairment. We found that AK extract reduced the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, phosphorylated-tau (p-tau), and the expression of inflammatory proteins in lipopolysaccharide- or amyloid-ß-treated cells. AK extract exhibited inhibitory activity of control specific binding on N-methyl-D-aspartate (NMDA) receptors. Scopolamine-induced AD models were used chronically in rats and acutely in mice. Relative to negative controls (NC), hippocampal choline acetyltransferase (ChAT) and B-cell lymphoma 2 (Bcl2) activity was increased in rats chronically treated with scopolamine and fed an AK extract-containing diet. In the Y-maze test, spontaneous alterations were increased in the AK extract-fed groups compared to NC. Rats administered AK extract showed increased escape latency in the passive avoidance test. In the hippocampus of rats fed a high-AK extract diet (AKH), the expression of neuroactive ligand-receptor interaction-related genes, including Npy2r, Htr2c, and Rxfp1, was significantly altered. In the Morris water maze assay of mice acutely treated with scopolamine, the swimming times in the target quadrant of AK extract-treated groups increased significantly to the levels of the Donepezil and normal groups. We used Tg6799 Aß-overexpressing 5XFAD transgenic mice to investigate Aß accumulation in animals. In the AD model using 5XFAD, the administration of AK extract decreased amyloid-ß (Aß) accumulation and increased the number of NeuN antibody-reactive cells in the subiculum relative to the control group. In conclusion, AK extract ameliorated memory dysfunction by modulating ChAT activity and Bcl2-related anti-apoptotic pathways, affecting the expression of neuroactive ligand-receptor interaction-related genes and inhibiting Aß accumulation. Therefore, AK extract could be a functional material improving cognition and memory.

Crude Saponin from Platycodon grandiflorum Attenuates Aß-Induced Neurotoxicity via Antioxidant, Anti-Inflammatory and Anti-Apoptotic Signaling Pathways.

Although Platycodon grandiflorum saponins exhibit many beneficial biological effects in various diseases and conditions, how they protect nerve cells against neurodegenerative diseases and Alzheimer's disease (AD) pathology is unknown. We investigated whether P. grandiflorum crude saponin (PGS) protects neurons from neurodegeneration caused by amyloid beta (Aß)-induced oxidative stress. Hippocampal neuron HT-22 cells were used in the in vitro experiment, and AD mice (5XFAD mice) were used as the in vivo model. Intracellular reactive oxygen species (ROS) was stained with DCF-DA and assessed using fluorescence microscopy. To elucidate the mechanism underlying neuroprotection, intracellular protein levels were assessed by western blotting. In 5XFAD mice, an animal model of AD, nerve damage recovery due to the induction of Aß toxicity was evaluated by histological analysis. PGS attenuates Aß-induced neurotoxicity by inhibiting Aß-induced reactive oxygen species (ROS) production and apoptosis in HT-22 cells. Furthermore, PGS upregulated Nrf2-mediated antioxidant signaling and downregulated NF-κB-mediated inflammatory signaling. Additionally, PGS inhibited apoptosis by regulating the expression of apoptosis-associated proteins. In addition, PGS ameliorated Aß-mediated pathologies, leading to AD-associated cognitive decline. Conclusions: Taken together, these findings suggest that PGS inhibits Aß accumulation in the subiculum and cerebral cortex and attenuates Aß toxicity-induced nerve damage in vitro and in vivo. Therefore, PGS is a resource for developing AD therapeutics.

Antioxidant and Anti-Melanogenic Activities of Heat-Treated Licorice (Wongam, Glycyrrhiza glabra × G. uralensis) Extract.

Melanin is a brown or black pigment that protects skin from ultraviolet radiation and reactive oxygen species (ROS). However, overproduction of melanin is associated with lentigines, melasma, freckles and skin cancer. Licorice has shown antioxidant, anti-tumor, anti-platelet, anti-inflammatory and immunomodulatory activities and is used as a natural treatment for skin whitening. We aimed to confirm the potential of Wongam, a new cultivar of licorice developed by the Rural Development Administration (RDA), as a whitening agent in cosmetics. In addition, we verified the effect of heat treatment on the bioactivity of licorice by comparing antioxidant and anti-melanogenic activities of licorice extract before and after heating (130 °C). The heat-treated licorice extract (WH-130) showed higher radical-scavenging activities in the ABTS+ (2,2'-azino-bis-(3-ethylbenzothiazolin-6-sulfonic acid) diammonium salt) and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays. In addition, WH-130 inhibited melanogenesis more effectively due to downregulation of tyrosinase in B16F10 melanoma cells than non-heated licorice extract. Moreover, heat treatment increased total phenolic content. In particular, isoliquiritigenin, an antioxidant and anti-melanogenic compound of licorice, was produced by heat treatment. In conclusion, WH-130, with increased levels of bioactive phenolics such as isoliquiritigenin, has potential for development into a novel skin whitening material with applications in cosmetics.

Neuroprotective Effects of Coreopsis lanceolata Flower Extract against Oxidative Stress-Induced Apoptosis in Neuronal Cells and Mice.

Coreopsis lanceolata L. is a perennial plant of the family Asteraceae, and its flower is known to contain flavonoids with various bioactivities. We evaluated the effect of Coreopsis lanceolata L. flower (CLF) extracts on H2O2-induced oxidative stress (OS) in neuronal cells and mouse neurons. The flowering part of CL was used as CLF1 (70% ethanol extract) and CLF2 (water extract), and 10 types of phenolic compounds were quantified using high-performance liquid chromatography. To evaluate the neuroprotective effects of CLF, the antioxidant activities of the extracts were measured, and the expression levels of antioxidant enzymes and proteins related to OS-induced apoptosis in neuronal cells and mouse neurons treated with the extracts were investigated. In the in vitro study, CLF ameliorated H2O2-induced oxidative stress and induced the expression of antioxidant enzymes in PC12 cells. Furthermore, CLF1 enhanced the expression of the Bcl-xL protein but reduced the expression of Bax and the cleavage of caspase-3. In the same manner, CLF1 showed neuroprotective effects against OS in vivo. Pretreatment with CLF1 (200 mg/kg) increased the Bcl-2 protein and decreased Bax compared with the 1-methyl-4-phenylpyridinium ion (MPP+)-treated C57BL/6 mice model group. Our results suggest that the protective effects of CLF1 on MPP+-induced apoptosis may be due to its anti-apoptotic activity, through regulating the expression of the Bcl-2 family. CLF1 exerts neuroprotective effects against OS-induced apoptosis in PC12 cells in a Parkinson's disease model mouse. This effect may be attributable to the upregulation of Bcl-2 protein expression, downregulation of Bax expression, and inhibition of caspase-3 activation. These data indicate that CLF may provide therapeutic value for the treatment of progressive neurodegenerative diseases.

Inhibitory effect of Streptococcus salivarius K12 and M18 on halitosis in vitro.

BACKGROUND: The aim of the study was to observe the antimicrobial activity of Porphyromonas gingivalis and Treponema denticola as well as the effect on reducing volatile sulfur compounds (VSCs). MATERIALS AND METHODS: After P. gingivalis and T. denticola were cultured with or without Streptococcus salivarius K12 and M18, VSCs were measured by Oral Chroma. In order to analyze the mechanism for malodor control, the antimicrobial activity of S. salivarius K12 and M18 against P. gingivalis and T. denticola was assessed. SPSS 21.0 was used for data analysis with the Kruskal-Wallis and Jonckheere-Terpstra tests. Mann-Whitney test was applied for post hoc analysis. RESULTS: P. gingivalis and T. denticola VSC levels were reduced by high concentrations of S. salivarius K12 and M18 during coculture. The concentrations were lower than those of single culture (p < .05). An antimicrobial effect was detected on P. gingivalis, and T. denticola by 50% S. salivarius K12 and M18. The spent culture medium and whole bacteria of S. salivarius K12 and M18 reduced the levels of VSCs below the amount in a single culture of P. gingivalis and T. denticola (p < .05). CONCLUSION: S. salivarius K12 and M18 decreased the levels of VSCs originating from P. gingivalis and T. denticola.

Erigeron annuus Protects PC12 Neuronal Cells from Oxidative Stress Induced by ROS-Mediated Apoptosis.

Reactive oxygen species (ROS), associated with oxidative stress, are involved in many biological processes such as apoptosis, necrosis, and autophagy. Oxidative stress might induce neuronal damage via ROS generation, causing neurodegenerative diseases. Erigeron annuus (EA) has antioxidant properties and could protect neurons from oxidative stress. In this study, we investigated the protective effect of the aerial parts (EAA) and flowers (EAF) from EA on ROS-mediated apoptosis in pheochromocytoma 12 cells. We quantified 18 types of phenolic compounds using high-performance liquid chromatography. Pretreatment of the cells with EAA and EAF attenuated ROS generation and induced the expression of antioxidant enzymes such as superoxide dismutase 2, catalase, and glutathione peroxidase. In addition, EAF reduced the expression of apoptotic proteins such as Bax/Bcl-xL, caspase-3, and caspase-8 to a greater extent than that with EAA. These results suggested that the protective effect of EAF against oxidative stress-induced apoptosis might be due to the prevention of ROS generation mediated by oxidative enzymes.

Cleavage of cytoplasm within the oligonucleate zoosporangia of allomyces macrogynus.

Allomyces macrogynus produces zoosporangia that discharge uninucleate zoospores after cleavage of multinucleate cytoplasm. Cleavage of cytoplasm within the oligonucleate zoosporangia of A. macrogynus was visualized by constructing three-dimensional models based on electron micrographs and confocal images. In oligonucleate zoosporangia, three adjacent nuclei can form three cleavage planes with a line of intersection of the planes. The position and boundary of the cleavage planes are thought to be determined by the relative positions of the nuclei. The establishment of three cleavage planes by cleavage membranes occurred sequentially, and the nuclear axis connecting the centers of two nuclei affected the development of cleavage membranes on each cleavage plane. In multinucleate zoosporangia, groups of three neighboring nuclei near the cell cortex may initiate the sequential establishment of cleavage planes and then may interact with the nuclei further from the cortex until the interactions of nuclei are propagated to the central region of the cytoplasm.

The effect of probiotics on prevention of common cold: a meta-analysis of randomized controlled trial studies.

BACKGROUND: Probiotics are currently under focus for their immune improvement function. Many studies have been performed to assess the potential efficacy of probiotics in allergic disease, viral disease, respiratory disease, as well as gastrointestinal disease. This study performed a systematic review to determine the effects of probiotics on the prevention of the common cold. METHODS: We searched MEDLINE (PubMed), EMBASE, CINAHL, and Cochrane CENTRAL for studies released through June 2011. Two authors independently extracted the data. To assess the risk of bias of included literatures, Cochrane Collaboration's risk of bias tool was used. RESULTS: We identified 10 studies in 7 articles. A total 2,894 participants, 1,588 in the probiotics group and 1,306 in the control group, were included. The effect of probiotics on the prevention of the common cold had a relative risk (RR) of 0.92 (95% CI, 0.85 to 1.00, I(2) = 26%). In the subgroup analysis, the RR of administration of probiotics for 3 months or less was 0.82 (95% CI, 0.70 to 0.97). The RR of administration of probiotics over 3 months was 1.00 (95% CI, 0.92 to 1.09). The RR of administration of probiotics without any active intervention (vitamin and mineral) was 0.87 (95% CI, 0.78 to 0.97). CONCLUSION: In this meta-analysis, there was marginal effect of probiotics on the prevention of the common cold. The results implied that probiotics had a modest effect in common cold reduction. The balance of benefit and harms needs to be considered when using probiotics for common cold prevention.

Cytokinesis of the binucleate zoosporangia of Allomyces macrogynus.

Allomyces macrogynus, a true fungus, produces zoosporangia which discharge uninucleate zoospores after cytoplasmic cleavage. Binucleate zoosporangia of A. macrogynus were induced and examined to understand the basic principles of cytokinesis associated with the multinucleate zoosporangia. Development of cleavage membranes was visualized by constructing three dimensional models based on electron micrographs and confocal images. Cleavage membranes on the cleavage plane showed asymmetric ingression from the cortex, but cleavage of cytoplasm was completed by the fusion of cleavage membranes with plasma membrane. Also, the position of the cleavage plane was continuously rotated until settled at the last stage. These studies suggest that the positions of the numerous cleavage planes within a multinucleate zoosporangium are continuously adjusted during development of cleavage membranes. The final settlement of cleavage planes would define the exact boundary of cleavage planes and the expansion of cleavage membranes toward the boundary could complete the cleavage of cytoplasm.