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Acer tegmentosum (ATM) has antioxidant and anti-adipogenic activity. However, few studies have investigated the pharmacological activity or mechanism of ATM as an antidepressant agent. We assessed the antidepressant effect of ATM in modulating menopausal depressive symptoms and its mechanisms in ovariectomized (OVX) and repeatedly stressed (RS) female rats. The female rats were randomly divided into four groups: (1) naïve normal (normal) group, (2) OVX + repeated stress + saline-treated (control) group, (3) OVX + repeated stress + ATM (100 mg•kg−1)-treated (ATM100) group and (4) OVX + repeated stress + ATM (400 mg•kg−1)-treated (ATM400) group. We performed a battery of tests, such as the forced swimming test (FST), the sucrose intake test, and social exploration. After behavior testing, serum corticosterone levels were examined, followed by immunohistochemical determination of c-Fos, tyrosine hydroxylase (TH), and interleukin-1 beta (IL-1β) expression in the brain. ATM administration was associated with significantly decreased immobility time in the FST. Also, the control group tended to have decreased sucrose intake and social exploration compared with the normal group. However, ATM treatment was associated with markedly increased sucrose intake and active social exploration. In the paraventricular nucleus, c-Fos and IL-1β expression were significantly decreased in the ATM400 group compared with the control group. Compared with the control group, high-dose ATM administration was also associated with markedly decreased expression of TH-immunoreactive neurons in the locus coeruleus. The study findings demonstrated that ATM treatment effectively decreased behavioral and pathophysiological depression-like responses.

Extraction from edible plants is a highly important process that has various biological functions. To maximize biological activity, extraction methods should facilitate optimal extraction of functional phytochemicals. In this study, the optimal hydrothermal extraction conditions of Acer tegmentosum were determined using response surface methodology (RSM), and HepG2 cells were treated with optimized extract and hydrogen peroxide. In a central composition design, the independent variables were extraction temperature (X1: 70&ndash, 90 &deg, C), extraction time (X2: 2&ndash, 6 h), and solvent-to-solid ratio (X3: 50&ndash, 150). The maximum total phenolic contents (276.70 &plusmn, 10.11 mg GAE/g) and DPPH (2,2-diphenyl-1-pictylhydrazyl) activity (33.45 &plusmn, 2.20%) of A. tegmentosum were estimated at optimized extraction conditions, as follows: X1: 89.34 &deg, C, X2: 7.36 h, X3: 184.09. Using the calculated extraction conditions, functional phytochemicals were extracted by hydrothermal extraction and freeze-dried. A. tegmentosum treatment (&gt, 10 &mu, g/mL) of HepG2 cells remarkably attenuated hydrogen-peroxide-inducible hepatic cellular death and reactive oxygen species production in vitro.

Ethnopharmacological relevance Acer tegmentosum Maxim (AT), the East Asian stripe maple, is an herb used to treat liver disease and is approved as a functional food in Korea. AT protects against hepatic disorders, atopic dermatitis, and diabetes mellitus. Aim of the study We explored the mechanism of the hepatoprotective effects of AT extract in in vitro and in vivo levels. Materials and methods AT extract from Acer tegmentosum Maxim was extracted by hot water. Hepatoprotective effects of AT extract were confirmed using carbon tetrachloride (CCl4)- or alcohol-induced mouse model, and H2O2- or alcohol-induced HepG2 (liver hepatocellular carcinoma cell line) cells by measuring GOT, GPT, TG, and MDA levels. Hematoxylin and eosin (H&E) staining was used to observe the pathological analysis. Cytotoxicity or protective effect of AT extract was confirmed using MTT assay in HepG2 cells. Antioxidant effect of AT extract was measured using DPPH or H2DCFDA assay. Mechanism study of antioxidant and autophagy was carried out using western blotting and immunofluorescence analysis. Results AT extract increased the viability of HepG2 cells treated with H2O2 and ethanol, and protected the liver against damage induced by CCl4 and alcohol. The AT extract increased the levels of nuclear respiratory factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The level of microtubule-associated protein light chain 3 (LC3)-Ⅱ, beclin-1, autophagy-related genes (Atg) such as Atg3 and Atg12-5 as markers of autophagy activation was also increased. Moreover, the AT extract increased activation of mitogen-activated protein kinase (MAPK), which regulated autophagy and HO-1. Conclusion Therefore, these results indicate that the AT extract has a hepatoprotective effect by increasing antioxidant activity and inducing autophagy.

Ethnopharmacological relevance Atopic dermatitis (AD) is a chronic and relapsing inflammatory condition characterized by pruritic and eczematous skin lesions that requires safe and effective pharmacological therapy. The bark of Acer tegmentosum Maxim trees has been used in Korean folk and traditional medicine to treat abscesses, surgical bleeding, liver diseases, and AD. Aim of study To investigate the therapeutic effect of A. tegmentosum , on a mouse model of Dermatophagoides farinae (Df)-induced AD. Methods Development of AD-like skin lesions was induced by repetitive skin contact with barrier-disrupted backs of NC/Nga mice with Df body ointment, and the effects of A. tegmentosum were evaluated on the basis of histopathological skin assessment results, ear swelling, and cytokine production in the dorsal skin. The component of A. tegmentosum , salidroside, inhibited the production of TSLP in KCMH-1 cells, which indicated that its production could be pharmacologically regulated. Results Topical application of A. tegmentosum for 1 week after Df body ointment challenge significantly reduced ear swelling and improved dorsal skin lesions. Suppression of dermatitis by combined therapy was accompanied by a decrease in the skin level of Th2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13, plasma levels of thymus and activation-regulated chemokine, and IgE. Induction of thymic stromal lymphopoietin, which leads to a systemic Th2 response, was also reduced in in vivo and in vitro by A. tegmentosum and salidroside. Conclusions Our findings suggest that A. tegmentosum treatment has a significant therapeutic effect on Df-induced AD-like skin lesions on NC/Nga mice through inhibition of thymic stromal lymphopoietin and IgE via a mechanism that may inhibit Th2-mediated immune responses. These results suggest that A. tegmentosum and salidroside may be useful tools for the treatment of AD.

The objective of this study was to investigate anticytotoxic and antioxidatative capacities of ethanol extracts from Acer tegmentosum Maxim (A. tegmentosum) stem in vitro. The extract at concentration of 200 ug/mL inhibited 10 and 20 ug/mL arsenic trioxide-induced cytotoxicity of HepG2 cells by 79.3 and 57.5%, respectively. The extract at concentration of 200 ug/mL inhibited 0.2 and 0.5 mM t-BHP-induced cytotoxicity of HepG2 cells by 66.3 and 35.7%, respectively. Antioxidative effects of the extract were examined via measurement of ABTS, superoxide, and peroxyl radical scavenging activities. ABTS radical scavenging activity of the extract was higher than that of -tocopherol. Superoxide scavenging activity of the extract was higher than that of catechin. Oxygen radical absorbance capacity of the extract was higher than that of ascorbic acid. Cupric reducing antioxidant capacity of the extract was higher than that of -tocopherol. The extract at concentrations of 100 and inhibited 10 mM t-BHP-induced lipid peroxidation of HepG2 cells by 38.2 and 80.7%, respectively. The extract prevented supercoiled DNA strand breakage induced by hydroxyl or peroxyl radical. Total phenolic and flavonoid contents of the extract at concentration of were 71.3 nmol/mL gallic acid and 18.8 nmol/mL catechin equivalents, respectively. Thus, strong cytoprotective and antioxidant effects of A. tegmentosum stem extract seem to be due to, at least in part, the prevention from free radicals-induced oxidation as well as high levels in polyphenolic contents.

Acer tegmentosum Maxim (AT) is a species of the maple genus, which is native to North-Eastern China and Korea. Traditionally, AT has been already used for pain relief in Korea. On the other hand, its antidepressant-like activity and related molecular mechanisms is not completely understood. Using the Forced Swimming Test (FST), the effects of a subacute treatment with AT(100, 200, and 400 mg/kg, p.o.) on the immobility and FST-induced changes to the immune parameters, cortisol, ACTH, and cytokine, in rats were investigated. The tendency of immobility showed a dose-dependent decrease in FST. The levels of cortisol, IL-6 and IL-1β in the peripheral blood were increased significantly after FST exposure. Overall, these results suggest that AT treatment can decrease the immobility time and the release of pro-inflammatory cytokines in the FST, suggesting that the anti-inflammatory effects of AT might be involved in the antidepressant-like effect.

The purpose of this study is to evaluate the antioxidant activities of extracts from Acer tegmentosum Maxim. (AT) and the ability of these extracts to reduce the serum alcohol concentration in rats administered alcohol. The total amount of polyphenols in hot water and ethanol extracts from AT were 71.93±2.2 μg/mg and 152.69 ±1.25 μg/mg, respectively, while the total amount of flavonoids in hot water and ethanol extracts from AT were 7.51±1.34 μg/mg and 5.01±0.83 μg/mg, respectively. FRAP values in AT extracts were 1.67～1.75 μM/μg. AT extracts were capable of directly scavenging DPPH and ABTS free radicals, with higher inhibitory activities for TBA. The hepatoprotective effect of hot water extracts from AT against ethanol-induced oxidative damage was investigated. Ethanol-induced damage on HepG2 liver cells were protected by hot water extracts from AT. Administration of hot water extracts from AT (200 mg/kg) had reduced serum alcohol levels in acute alcohol-treated rats. These results indicate that AT extracts can be protective against alcohol-induced toxicity, potentially through its antioxidant properties.

While Acer tegmentosum M. (AT) has been widely used as a popular folk remedy to prevent or treat liver diseases in Korea, the scientific evidences for the usage of AT against liver disease are poorly documented. To address this issue, we compared hepatoprotection of hot water extract (WEAT) from three parts of AT, boughs (E1), twigs (E2), and leaves (E3), on CCl4-induced acute hepatic injury in mice by way of morphometric and biochemical examination: liver function test, antioxidant enzymes activity of liver, histopathological and ultrastructural examination of liver, and antioxidant capacity (DPPH assay) of WEAT. We found that only oral intake group of WEAT-boughs showed significant differences in aspartate transaminase (AST), alanine transaminase (ALT) levels and glutathione peroxidase (GPx) activities as compared to CCl4 control group, whereas the glutathione levels were significantly low in all WEAT-pretreated groups. Consistently, histopathological and ultrastructural findings displayed hepatoprotection in the order of WEAT-boughs >WEAT-twigs>WEAT-leaves. Collectively, these results indicate that of three WEAT, WEAT-bough extract has the highest hepatoprotection against CCl4-induced acute hepatic injury in mice via the possible regulation of antioxidant enzyme activities in liver.

Aim of study Acer tegmentosum has been traditionally used for folk medicine to treat hepatic disorders such as hepatitis, hepatic cancer, and hepatic cirrhosis. In this study, we demonstrate the ethno-pharmacological activity of Acer tegmentosum in in vitro and in vivo inflammatory conditions. Results The 70% ethanol extract (At-EE) of Acer tegmentosum dose-dependently diminished the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, and prostaglandin (PG)E2, in lipopolysaccharide (LPS)-activated RAW264.7 cells and peritoneal macrophages, by a transcriptional mechanism. At-EE also suppressed the activation of nuclear factor (NF)-κB, activator protein (AP)-1, and cAMP-responsive element binding (CREB), and simultaneously blocked their upstream inflammatory signalling cascades, including Akt, p38, and JNK. Furthermore, At-EE protected against LPS-induced cell death induced by reactive oxygen species (ROS) and reactive nitrogen species (RNS) and neutralized reactive species generation. In agreement with the in vitro results, orally administered At-EE strongly ameliorated ear oedema formation induced by arachidonic acid. Conclusion At-EE displays strong anti-inflammatory activities in vitro and in vivo, contributing to its major ethno-pharmacological role such as anti-hepatitis remedy and may be applicable to novel anti-inflammatory therapeutics.

Acer tegmentosum is a type of deciduous tree that grows in Korea. It has been used in traditional medicine for the treatment of hepatic disorders. In this study, chromatography fractionation and isolation have been successfully used to yield 15 compounds, including 10 flavonoids, 4 phenylethyl glycosides, and 1 other glycoside. Their structures were determined on the basis of their physical and spectral properties [(1)H and (13)C nuclear magnetic resonance (NMR) and mass spectrometry (MS)] and by comparison of these results to similar data in the literature. The total peroxyl radical-scavenging capacity of each isolated compound was evaluated. Among them, the most active components belong to the flavonoids. Among these, quercitrin (1), 6-hydroxy-quercetin-3-O-galactose (6), and (+)-catechin (8) showed stronger activity than the positive control Trolox.

Fraxin isolated from Acer tegmentosum is reported to exert potent anti-oxidative stress action. However, pharmacological activities of fraxin remain to be elucidated. This study investigated the potential hepatoprotective effects of fraxin and the underlying signaling mechanism involved. Treatment with fraxin significantly lowered the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a CCl4-induced hepatotoxicity rat model. In the fraxin-treated group, glutathione (GSH) significantly increased, while the malondialdehyde (MDA) in the liver significantly decreased. Fraxin also showed radical-scavenging activity. Furthermore, it significantly reduced the t-BHP-induced cytotoxicity and production of reactive oxygen species (ROS) in Hep G2. Fraxin protected Hep G2 cells through Nrf2 pathway-dependent HO-1 expression. The results of this study indicate that fraxin shows potent hepatoprotective effects in vitro and in vivo, presumably through direct antioxidant activity and the Nrf2-mediated antioxidant enzyme system.

The stem of Acer tegmentosum has been widely used in Korea for the treatment of hepatic disorders. In this study, we investigated the bone protective effect of water extract of the stem of Acer tegmentosum (WEAT). We found that WEAT inhibits osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclast differentiation. In osteoclast precursor cells, WEAT inhibited RANKL-induced activation of JNK, NF-κB, and cAMP response element-binding protein, leading to suppression of the induction of c-Fos and nuclear factor of activated T cells cytoplasmic 1, key transcription factors for osteoclast differentiation. In addition, WEAT inhibited bone resorbing activity of mature osteoclasts. Furthermore, the oral administration of WEAT reduced RANKL-induced bone resorption and trabecular bone loss in mice. Taken together, our study demonstrates that WEAT possesses a protective effect on bone destruction by inhibiting osteoclast differentiation and function.

The chromatographic separation of methanol extract from Acer tegmentosum twigs led to the isolation of one phytosterol and five phenolic compounds. Using spectroscopic methods, the structures of these compounds were determined as β-sitosterol 3-O-β-D-glucopyranoside (1), ρ-hydroxyphenylethyl-O-β-D-glucopyranoside (Salidroside) (2), ρ-hydroxyphenylethyl alcohol (tyrosol) (3), 6’-O-galloylsalidroside (4), Quercetin 3-O-β-D-glucopyranoside (5), Quercetin (6). Compounds 1, 3, 4, 5 and 6 were isolated from the plant for the first time, but we also found that 2 and 4 were major compounds (high contents). We measured the antioxidant activity (radical/superoxide scavenging activity) and anti-inflammatory activity (nitric oxide (NO) scavenging activity in RAW 264.7, BV2 cell lines). The ethyl acetate fraction and compounds 4, 6 had both activities, but the hexane fraction and 2 had only anti-inflammatory activity. Together, all data indicate that A. tegmentosum extract is a source of functional food and treatments for neurodegenerative diseases. Key words: Acer tegmentosum, antioxidant activity, anti-inflammatory activity, compound.