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The fruits, leaves, and roots of Cudrania tricuspidata have been reported to contain large amounts of vitamin B, vitamin C, and flavonoids. They exhibit various physiological activities such as antitumor and anti-inflammatory effects. However, the hepatoprotective effects of C. tricuspidata extracts against oxidative stress-mediated liver injury have not yet been investigated. We thus examined whether C. tricuspidata leaf extracts (CTEs) protect against oxidative stress-mediated liver injury in vitro and in vivo and elucidated the underlying mechanism. The cytoprotective effects of CTE through the NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) activation were presented and measured by biochemical analysis in HepG2 cells. To assess the protective effects of CTE in vivo , mice were administered with CTE (250 and 500 mg/kg; 5 days; p.o.) before a single dose of acetaminophen (APAP) (300 mg/kg; 24 h; i.p.). CTE increased ARE luciferase activity when compared with extracts of other parts of C. tricuspidata. CTE upregulated nuclear translocation of Nrf2 and its target gene expression. In addition, CTE inhibited the generation of reactive oxygen species (ROS) and cell death induced by arachidonic acid (AA) and iron (Fe) treatment in primary hepatocytes or HepG2 cells. The cytoprotective effects of CTE against oxidative stress might be due to kaempferol, the major flavonoid present in CTE. Kaempferol pretreatment blocked AA+Fe-induced ROS production and reversed glutathione depletion, which in turn led to decreased cell death. Furthermore, the protective effects of CTE against liver injury induced by excess APAP in mice or primary hepatocytes were observed. CTE could be a promising therapeutic candidate against oxidative stress-induced liver injury.

Background: Prolonged hyperuricemia is associated with kidney disease or gouty arthritis. Whether Yokuininto, a commercially available Kampo medicine that has been used for osteoarthritis or rheumatoid arthritis, can exhibit anti-hyperuricemic and inflammatory effects remains elusive. In the present study, Yokuininto exerts multiple homeostatic action on serum uric acid (sUA) levels by blocking pro-inflammatory cytokine activities and inducing uricosuric function with anti-renal injury functions., Methods: The sUA was measured in potassium oxonate (PO)-administered mice. Renal transporter uptake assays were performed using HEK293 cells overexpressing OAT1, OCT2 or OAT3, MDCKII cells overexpressing BCRP, and Xenopus oocytes overexpressing OAT3 or URAT1. Immunoblot and ELISA assays were performed to detect the molecules (OAT3, GLUT9, XO, NGAL, KIM-1 and IL-1α) in various human kidney cell lines. Cell viability analysis was performed to evaluate the cytotoxicity of Yokuininto [Ephedrine + pseudoephedrine 21.94%; Paeoniflorin 35.40% and Liquiritin 16.21% relatively measured by the ratios (HR-MS2 intensity / HR-MS1 intensity)]., Results: Yokuininto (300 mg/kg) significantly reduced sUA by approximately 44% compared to that of PO-induced mice. The OAT3 levels were decreased in PO-induced hyperuricemic condition, whereas the GLUT9 transporter levels were markedly increased. However, PO did not alter the levels of URAT1. Yokuininto significantly inhibited the lipopolysaccharide (LPS)-induced secretion of IL-1α by approximately 63.2% compared to the LPS-treated macrophages. In addition, Yokuininto inhibited nitric oxide synthesis by approximately 33.7 (500 µg/mL) and 64.6% (1000 µg/mL), compared to that of LPS-treated macrophages. Yokuininto markedly increased xanthine oxidase inhibition activity. Furthermore, interleukin-1α (IL-1α), a pro-inflammatory cytokine, elevated neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) activities in LLC-PK1 cells. Expression of renal inflammatory biomarkers, NGAL and KIM-1, was reduced under the Yokuininto treatment by 36.9 and 72.1%, respectively., Conclusions: Those results suggest that Yokuininto may suppress inflammation and protect against kidney dysfunction in hyperuricemia. The present findings demonstrated that Yokuininto lowered sUA through both increased uric acid excretion and decreased uric acid production. Our results may provide a basis for the protection of prolonged hyperuricemia-associated kidney injury with uric acid-lowering agents such as Yokuininto.

We evaluated the antioxidant and antibacterial activity of hexnane, ethyl acetate, acetone, methanol, ethanol, and water extracts of the Quercus acuta leaf. The antioxidant properties were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, reducing power, and total phenolic content. Antibacterial activity was assessed against general infectious pathogens, including antibiotic-resistant clinical isolates. The methanolic extract showed the highest DPPH radical scavenging activity and total phenolic content, while the reducing power was the highest in the water extract. The ethyl acetate extract showed the best antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Additionally, it displayed antibacterial activity against Staphylococcus aureus KCTC1928, Micrococcus luteus ATCC 9341, Salmonella typhimurium KCTC 1925, Escherichia coli KCTC 1923, and eight MRSA strains. These results present basic information for the possible uses of the ethanolic and ethyl acetate extracts from Q. acuta leaf in the treatment of diseases that are caused by oxidative imbalance and antibiotic-resistant bacterial infections. Six active compounds, including vitamin E, which are known to possess antioxidant and antibacterial activity, were identified from the extracts. To the best of our knowledge, this is the first study that reports the chemical profiling and antibacterial effects of the various QA leaf extracts, suggesting their potential use in food therapy or alternative medicine.

Objectives: The aim of this study was to systematically review data regarding pharmacokinetic (PK)-pharmacodynamic (PD) parameters from randomized controlled trials relating to interactions between herbal medicines and warfarin., Methods: Three electronic databases were searched to identify relevant trials. Two reviewers independently performed the study selection and data extraction. The risk of bias and reporting quality were also assessed independently by two reviewers using the Cochrane risk of bias tool and the consolidated standards of reporting trials (CONSORT). Outcomes were measured for all reported PK-PD parameters and adverse events., Results: Nine randomized controlled trials met our inclusion criteria. Most of the included studies were unclear regarding the risk of bias and had a low quality of methodology. Using CONSORT, the reporting percentages for the articles ranged from 36.5% to 61.5% and the mean percentage for all articles was 45.6%. St John's wort and echinacea affected the PK parameters of warfarin. Ginseng, ginger, garlic, and cranberry had no significant effect on the PK parameters. American ginseng altered the PD parameters of warfarin. St John's wort, ginseng, Korea red ginseng, ginkgo, ginger, garlic, aged garlic, and echincea did not significantly alter the PD parameters. Studies of ginkgo and cranberry showed conflicting results on the PK parameters and PD parameters, respectively. The incidence of adverse events in all trials was low and no major adverse events were reported., Conclusions: It was difficult to determine whether ten herbal medicines had significant effects on the PK-PD parameters of warfarin. Low quality of evidence, different compounds within and different compositions of the herbs, and methodological limitations of the crossover study, which is a clinical study in which subjects receive a sequence of different interventions, made it difficult to form conclusions. Additional studies that remedy these vulnerabilities are necessary to verify these results.

Camellia japonica L. is a plant of which the seeds are used as a folk medicine, and it is native to South Korea, Japan and China. In previous study, triterpenes, flavonoids, tannins and fatty acids which have antiviral, antioxidant and anti inflammatory activity were reported from C. japonica leaf and flower. In Korea, the seed from this plant is used as a traditional medicine and in folk remedies for the treatment of bleeding and inflammation. However, the major issue associated with the use of the seed as a medicinal and/or functional food ingredient is its application to the pharmaceutical and food industry. First, the productivity of seed extract is very much less than that of the leaf. Second, the beneficial usage of the seed extract as an alternative medicine and functional source is not yet clear. Thus, in this study, we focused on another part of the plant, the leaf, and found that the extract of Camellia japonica leaf has a high concentration of vitamin E, rutin and other biologically active compounds related to hyperuricemia. We aimed to investigate the biological activities, namely the antioxidant activities, xanthine oxidase (XO) inhibitory activity and anti‑hyperuricemic effects of extract from C. japonica leaf and the phytochemicals contained therein. Ethanol extracts of C. japonica leaf (ECJL) were prepared, and the extract was used with respect to antioxidant activities, total phenolic contents and XO inhibitory activity. The in vivo XO inhibitory activity and anti‑hyperuricemic effects of the extract were evaluated in mice with potassium oxonate‑induced hyperuricemia. To clarify the marker compounds that are responsible for the anti‑hyperuricemic effects, several key constituents were identified using gas chromatography‑mass spectrometry (GC‑MS) and and liquid chromatography-mass spectrometry (LC-MS). ECJL was found to have strong antioxidant activities, and in vitro XO inhibitory activity. The results of the in vivo experiments using mice demonstrated that ECJL at the doses of 100 and 300 mg/kg inhibited hepatic XO activity and significantly attenuated hyperuricemia. To the best of our knowledge, the present study is the first report on the XO inhibitory and anti-hyperuricemic effects of ECJL, which can be therapeutically applied in the treatment of hyperuricemia and gout.

We previously reported the clinical profile of processed Aconitum carmichaelii (AC, Aconibal(®)), which included inhibition of cytochrome P450 (CYP) 2E1 activity in healthy male adults. CYP2E1 is recognized as the enzyme that initiates the cascade of events leading to acetaminophen (APAP)-induced toxicity. However, no studies have characterized its role in APAP-induced hepatic injury. Here, we investigated the protective effects of AC on APAP-induced hepatotoxicity via mitochondrial dysfunction. AC (5-500 μg/mL) significantly inhibited APAP-induced reduction of glutathione. In addition, AC decreased mitochondrial membrane potential (Δψm) and B-cell lymphoma 2 (Bcl-2)-associated X protein levels (% change 46.63) in mitochondria. Moreover, it increased Bcl-2 (% change 55.39) and cytochrome C levels (% change 38.33) in mitochondria, measured using immunofluorescence or a commercial kit. Furthermore, cell membrane integrity was preserved and nuclear fragmentation inhibited by AC. These results demonstrate that AC protects hepatocytes against APAP-induced toxicity by inhibiting mitochondrial dysfunction., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Monoamine oxidase (MAO) catalyzes the oxidative deamination of monoamines including dopamine (DA). MAO expression is elevated in Parkinson's disease (PD). An increase in MAO activity is closely related to age, and this may induce neuronal degeneration in the brain due to oxidative stress. MAO (and particularly monoamine oxidase B (MAO-B)) participates in the generation of reactive oxygen species (ROS), such as hydrogen peroxide that are toxic to dopaminergic cells and their surroundings. Although the polyphenol-rich aqueous walnut extract (JSE; an extract of Juglandis Semen) has been shown to have various beneficial bioactivities, no study has been dedicated to see if JSE is capable to protect dopaminergic neurons against neurotoxic insults in models of PD. In the present study we investigated the neuroprotective potential of JSE against 1-methyl-4-phenylpyridinium (MPP⁺)- or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicities in primary mesencephalic cells and in a mouse model of PD. Here we show that JSE treatment suppressed ROS and nitric oxide productions triggered by MPP⁺ in primary mesencephalic cells. JSE also inhibited depletion of striatal DA and its metabolites in vivo that resulted in significant improvement in PD-like movement impairment. Altogether our results indicate that JSE has neuroprotective effects in PD models and may have potential for the prevention or treatment of PD.

Background: Gleditsia sinensis thorns have been widely used in traditional Korean medicine for the treatment of several diseases, including obesity, thrombosis, and tumor-related diseases. The aim of the study is to determine the antiangiogenic effect of Gleditsia sinensis thorns in vitro and in vivo in a bid to evaluate its potential as an anticancer drug., Methods: Ethanol extract of Gleditsia sinensis thorns (EEGS) were prepared and used for in vitro and in vivo assays. In vitro antiangiogenic effect of EEGS was determined in HUVEC primary cells by cell migration and tube formation assays. In vivo antiangiogenic effect of EEGS was determined by measuring vessel formation and vascular endothelial cells migrating into the implanted matrigels in nude mice. The angiogenesis-related proteins of which expression levels were altered by EEGS were identified by proteomic analysis., Results: EEGS exerted a dose-dependent antiproliferative effect on HUVEC cells without significant cytotoxicity. Angiogenic properties, such as cell migration and tube formation, were significantly inhibited by EEGS in a dose-dependent manner. New vessel formation was also suppressed by EEGS, as determined by the directed in vivo angiogenesis assays in nude mice. EEGS reduced the expression of proangiogenic proteins, endothelin 1 and matrix metallopeptidase 2, in HUVEC cells., Conclusions: Our findings suggest that EEGS can inhibit angiogenesis by down-regulating proangiogenic proteins, and therefore it should be considered as a potential anticancer drug targeting tumor-derived angiogenesis.

To determine the effects of kimchi extracts at different temperatures on larval development, Ascaris suum eggs were mixed with soluble part of 7 different brands of commercially available kimchi and preserved at either 5℃ or 25℃ for up to 60 days. A. suum eggs incubated at 25℃ showed marked differences in larval development between kimchi extract and control group. While all eggs in the control group completed embryonation by day 21, only 30% of the eggs in the kimchi extract group became embryonated by day 36 and about 25% never became larvated even at day 60. At 5℃, however, none of the eggs showed larval development regardless of the incubation period or type of mixture group. To determine the survival rate of A. suum eggs that showed no embryonation after being preserved at 5℃, eggs preserved in kimchi extracts for 14, 28, and 60 at 5℃ were re-incubated at 25℃ for 3 weeks in distilled water. While all eggs in the control group became larvated, eggs in the kimchi extract group showed differences in their embryonation rates by the incubation period; 87.4 % and 41.7% of the eggs became embryonated after being refrigerated for 14 days and 28 days, respectively. When refrigerated for 60 days, however, no eggs mixed in kimchi extract showed larval development. Our results indicate that embryogenesis of A. suum eggs in kimchi extract was affected by duration of refrigeration, and that all eggs stopped larval development completely in kimchi kept at 5℃ for up to 60 days.

HT008-1 is one of the most effective multiherb mixtures that have neuroprotective effects in traditional Korean medicine. The purpose of this study was to conduct a clinical trial of the efficacy of HT008-1 on the neuropsychological functioning and quality of life (QoL) in cognitively intact adults. One hundred and eighteen male (n - 42) and female (n = 76) volunteers who reported no history of dementia or significant neurocognitive impairments and obtained Korean Version of Mini Mental State Examination total scores of at least 24 were examined via an 8-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel group, clinical trial. Participants were randomly assigned to receive either HT008-1 (n = 59) or placebo (n = 59) for 8 weeks. Efficacy measures consisted of participants' performance scores from pretreatment baseline to those obtained just before termination of treatment on standardized neuropsychological measures from the subsets of Wechsler Memory Scale-III (WMS-III). QoL was assessed by subjective questionnaires WHOQoL-Bref about five categories. Participants who scored in the lower third of the Auditory recognition delayed at baseline and received HT008-1 exhibited improvement on the WMS-III Auditory recognition delayed subtest compared with placebo controls. The HT008-1 group also improved on general health scores in the QoL test.