Exploring immunoregulatory properties of a phenolic-enriched maple syrup extract through integrated proteomics and in vitro assays.

Our laboratory has established a comprehensive program to investigate the phytochemical composition and nutritional/medicinal properties of phenolic-enriched maple syrup extract (MSX). Previous studies support MSX's therapeutic potential in diverse disease models, primarily through its anti-inflammatory effects. We recently demonstrated MSX's ability to regulate inflammatory signaling pathways and modulate inflammatory markers and proteins in a lipopolysaccharide (LPS)-induced peritonitis mouse model. However, MSX's immunoregulatory properties remain unknown. Herein, we investigated MSX's immunoregulatory properties for the first time using an integrated approach, combining data-dependent acquisition (DDA) and data-independent acquisition (DIA) strategies in a proteomic analysis of spleen tissue collected from the aforementioned peritonitis mouse model. Additionally, we conducted immune cell activation assays using macrophages and T lymphocytes. The DIA analysis unveiled a distinctive expression pattern involving three proteins-Krt83, Thoc2, and Vps16-which were present in both the control and MSX-treated groups but absent in the LPS-induced model group. Furthermore, proteins Ppih and Dpp9 exhibited significant reductions in the MSX-treated group. Ingenuity pathway analysis indicated that MSX may modulate several critical signaling pathways, exerting a suppressive effect on immune responses in various cell types involved in both innate and adaptive immunity. Our in vitro cell assays supported findings from the proteomics, revealing that MSX significantly reduced the levels of interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) in LPS-stimulated human macrophage cells, as well as the levels of IL-2 in anti-CD3/anti-CD28-induced Jurkat T cells. Taken together, our investigations provide evidence that MSX exerts immune regulatory effects that impact both innate and adaptive immunity, which adds to the data supporting MSX's development as a functional food.

Uncovering the anti-inflammatory mechanisms of phenolic-enriched maple syrup extract in lipopolysaccharide-induced peritonitis in mice: insights from data-independent acquisition proteomics analysis.

Our group has previously reported on the phytochemical composition and biological activities of a phenolic-enriched maple syrup extract (MSX), which showed promising anti-inflammatory effects in several disease models including diabetes and Alzheimer's disease. However, the efficacious doses of MSX and its molecular targets involved in the anti-inflammatory effects are not fully elucidated. Herein, the efficacy of MSX in a peritonitis mouse model was evaluated in a dose-finding study and the underlying mechanisms were explored using data-independent acquisition (DIA) proteomics assay. MSX (at 15, 30 and 60 mg kg-1) alleviated lipopolysaccharide-induced peritonitis by reducing the levels of pro-inflammatory cytokines including interleukin-1 beta (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α) in the serum and major organs of the mice. Furthermore, DIA proteomics analyses identified a panel of proteins that were significantly altered (both up- and down-regulated) in the peritonitis group, which were counteracted by the MSX treatments. MSX treatment also modulated several inflammatory upstream regulators including interferon gamma and TNF. Ingenuity pathway analysis suggested that MSX may modulate several signaling pathways in the processes of initiation of cytokine storm, activation of liver regeneration, and suppression of hepatocyte apoptosis. Together, these proteomic and in vivo findings indicate that MSX could regulate inflammation signaling pathways and modulate inflammatory markers and proteins, providing critical insight to its therapeutic potential.

UPLC-QTOF-MS-based metabolomics and chemometrics studies of geographically diverse Acer truncatum leaves: A traditional herbal tea in Northern China.

Traditionally in Northern China, Acer truncatum leaves (ATL) have been used as herbal tea, now consumed worldwide. Few studies have reported ATL metabolites from different areas and their correlation with the environment. Thus, metabolomic analyses were conducted on ATL collected from twelve locations throughout four environmental zones in Northern China to understand the phytochemical differences with regards to environmental conditions. Sixty-four compounds, mostly flavonoids (FLAs) and gallic acid-containing natural products (GANPs), were characterized, including 34 previously unreported constituents from A. truncatum. Twenty-two markers were useful to differentiate ATL from the four environmental zones. Humidity, temperature, and sunshine duration are the predominant factors affecting FLAs and GANPs levels. Sunshine duration was positively correlated with eriodictyol (r = 0.994, p < 0.01), and humidity negatively with epicatechin gallate (r = -0.960, p < 0.05). These findings provide insights into ATL phytochemistry, aiding cultivation of A. truncatum tea with higher potential health benefits.

UPLC-ESI-Q-TOF-MSE-based metabolomics analysis of Acer mono sap and evaluation of osteogenic activity in mouse osteoblast cells.

Investigation of phytochemicals and bioactive molecules is tremendously vital for the applications of new plant resources in chemistry, food, and medicine. In this study, the chemical profiling of sap of Acer mono (SAM), a Korean syrup known for its anti-osteoporosis effect, was performed using UPLC-ESI-Q-TOF-MSE analysis. A total of 23 compounds were identified based on the mass and fragmentation characteristics and most of the compounds have significant biomedical applications. The in vitro antioxidant assessment of SAM indicated excellent activity by scavenging DPPH and ABTS-free radicals and were found to be 23.35 mg mL-1 and 29.33 mg mL-1, respectively, as IC50 concentrations. As well, the in vitro proliferation effect of the SAM was assessed against mouse MC3T3-E1 cells, and the results showed that the SAM enhanced the proliferation of the cells, and 12.5 mg mL-1 and 25 mg mL-1 of SAM were selected for osteogenic differentiation. The morphological analysis clearly evidenced the SAM enhanced the osteogenic activity in MC3T3-E1 cells by the increased deposition of extracellular calcium and nodule formation. Moreover, the qRT-PCR analysis confirmed the increased expression of osteoblast marker gene expression including ALP, osteocalcin, osteopontin, collagen1α1, Runx2, and osterix in SAM-treated MC3T3-E1 cells. Together, these results suggest that SAM possesses osteogenic effects and can be used for bone regeneration and bone loss-associated diseases such as osteoporosis.

Optimization technology and kinetic studies of Acer truncatum seed oil saponification and crystallization separation of nervonic acid.

Acer truncatum seed oil (ATSO) contains abundant unsaturated fatty acids, with significant quantities of nervonic acid (NA, > 5%), which was authenticated as a new food resource in China. For the sake of minimizing animal consumption and the importance of NA for human health, extraction of NA from plants has become a research hotspot. In the present study, three extraction factors were determined to significantly influence the saponification reaction based on single-factor experiments: NaOH dosage, reaction time, and reaction temperature. These three factors were used to further optimize the saponification process through the response surface methodology, and the highest yield of mixed fatty acids was 83.12%. Moreover, the activation energy (40.8228 kJ/mol), the pre-exponential factor [2.568 × 106 m3 /(kmol·min)], and the kinetic equation [rA = kcA cB = 2.568 × 106 ·exp(- 4970 . 1 T ) $\frac{{{\rm{4970}}{\rm{.1}}}}{{\rm{T}}})$ cA cB ] of the ATSO saponification reaction were determined by combining the chemical reaction rate equation of the elementary reaction, the Arrhenius equation, and the NaOH concentration in the substrate. Finally, the mixed fatty acids of ATSO were crystallized by triple-stage low-temperature crystallization, and we achieved 25.05% purity for NA. This study provides a technological basis and strategy for specific fatty acid production from ASTO, as well as other vegetable oils important in the field of food and health supplement products. PRACTICAL APPLICATION: Nervonic acid (NA) is an essential component of neural cells and neural tissue, and it is vital for maintaining the normal work of nerve tissues in organisms and promotes neurodevelopment. NA has traditionally been mainly obtained from shark hunting, which is now restricted due to an international ban on shark fishing. The alternative way to produce NA cheaply and in large quantities is from plant sources. The techniques utilized in this study provide an effective method of NA separation from Acer truncatum seed oil for industrial production.

Inhibitory Effect of Acer truncatum Bunge Seed Coat Extract on Fatty Acid Synthase, Differentiation and Lipid Accumulation in 3T3-L1 Adipocytes.

Acer truncatum Bunge is now widely cultivated throughout the world. Fatty acid synthase (FAS) is a potential target in the treatment of both obesity and cancer. Only a few FAS inhibitors have been reported. In this study, the inhibitory effect of A. truncatum seed coat (ESA) on FAS and the inhibition mechanisms were investigated using a FAS activity assay and an enzyme kinetics study. The main chemicals of ESA were analyzed with UPLC-MS/MS. The effects of ESA on 3T3-L1 adipocyte differentiation and lipid accumulation were investigated using Oil red O staining. We first identified seven main compounds (quinic acid, malic acid, gentisic acid, procyanidin dimer, procyanidin trimer, catechin, and quercetin) from 50% ethanol extracts of seed coats of A. truncatum (ESAs), which were then found to inhibit 3T3-L1 adipocyte differentiation at the concentration of 50 µg/mL. ESA obviously reduced the visible triglyceride droplets accumulation, and dramatically decreased the number of the adipocytes at a comparatively high concentration. It is suggested that the effects are due to the inhibition of FAS by ESA; FAS activity is inhibited by ESA at a half inhibition concentration (IC50) of 0.57 µg/mL, which is lower than that of classically known FAS inhibitors. Meanwhile, ESA displayed different inhibition kinetics and reacting sites for FAS. These results provide new clues for the development of novel products for obesity treatment and a scientific basis for the full use of byproducts for future industrial production of vegetable oil.

Acer tataricum subsp. ginnala Inhibits Skin Photoaging via Regulating MAPK/AP-1, NF-κB, and TGFß/Smad Signaling in UVB-Irradiated Human Dermal Fibroblasts.

Skin, the organ protecting the human body from external factors, maintains structural and tensile strength by containing many collagen fibrils, particularly type I procollagen. However, oxidative stress by ultraviolet (UV) exposure causes skin photoaging by activating collagen degradation and inhibiting collagen synthesis. Acer tataricum subsp. ginnala extract (AGE) is a herbal medicine with anti-inflammatory and anti-oxidative effects, but there is no report on the protective effect against skin photoaging. Therefore, we conducted research concentrating on the anti-photoaging effect of Acer tataricum subsp. ginnala (AG) in UVB (20 mJ/cm2)-irradiated human dermal fibroblasts (HDF). Then, various concentrations (7.5, 15, 30 µg/mL) of AGE were treated in HDF for 24 h following UVB irradiation. After we performed AGE treatment, the matrix metalloproteinase1 (MMP1) expression was downregulated, and the type I procollagen level was recovered. Then, we investigated the mitogen-activated protein kinases/activator protein 1 (MAPK/AP-1) and nuclear factor-κB (NF-κB) pathway, which induce collagen breakdown by promoting the MMP1 level and pro-inflammatory cytokines. The results indicated that AGE downregulates the expression of the MAPK/AP-1 pathway, leading to MMP1 reduction. AGE inhibits nuclear translocation of NF-κB and inhibitor of nuclear factor-κB (IκB) degradation. Therefore, it downregulates the expression of MMP1 and pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 increased by UVB. Besides, the TGFß/Smad pathway, which is mainly responsible for the collagen synthesis in the skin, was also analyzed. AGE decreases the expression of Smad7 and increases TGFßRII expression and Smad3 phosphorylation. This means that AGE stimulates the TGFß/Smad pathway that plays a critical role in promoting collagen synthesis. Thus, this study suggests that AGE can be a functional material with anti-photoaging properties.

Acer tegmentosum Maxim Inhibits Adipogenesis in 3t3-l1 Adipocytes and Attenuates Lipid Accumulation in Obese Rats Fed a High-Fat Diet.

We investigated the effect of Acer tegmentosum Maxim (ATM) on adipocyte differentiation in 3T3-L1 cells and anti-obesity properties in obese rats fed a high-fat diet (HFD). Cellular lipid content in DMI (dexamethasone, 3-isobutyl-1-methylxanthine, and insulin mixture)-treated cells increased, while ATM treatment caused a significant reduction in lipid accumulation in differentiated 3T3-L1 cells. ATM (60 ug/mL) caused inhibition of adipogenesis via down-regulation of the CCAAT/enhancer binding protein ß (C/EBPß) (48%), C/EBPα (66%), and peroxisome proliferator-activated receptor γ (PPARγ) (64%) expressions in 3T3-L1 cells. Moreover, ATM induced a decrease in the expressions of adipocyte-specific genes, such as adipocyte fatty acid-binding protein-2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL). Protein kinase B (Akt) and glycogen synthase kinase 3ß (GSK3ß) phosphorylation was also decreased by ATM treatment of 3T3-L1 adipocytes. We investigated the anti-obesity effects of ATM on HFD-induced obese rats. Rats fed with an HFD demonstrated elevations in body weight gain, while the administration of ATM reversed body weight (BW) gains and adipose tissue weights in rats fed an HFD. ATM supplementation caused a decrease in the circulating triglyceride and total cholesterol levels and led to inhibition of lipid accumulation in the adipose tissues in HFD-induced obese rats. Epididymal fat exhibited significantly larger adipocytes in the HFD group than it did in the ATM-treated group. These results demonstrate that ATM administration caused a reduction in adiposity via attenuation in adipose tissue mass and adipocyte size.

Neuroprotective effects of Acer palmatum thumb. leaf extract (KIOM-2015E) against ischemia/reperfusion-induced injury in the rat retina.

Purpose: The present study aimed to determine whether the administration of Acer palmatum thumb. leaf extract (KIOM-2015E) protects against the degeneration of rat retinal ganglion cells after ischemia/reperfusion (I/R) induced by midbrain cerebral artery occlusion (MCAO). Methods: Sprague-Dawley rats were subjected to 90 min of MCAO, which produces transient ischemia in both the retina and brain due to the use of an intraluminal filament that blocks the ophthalmic and middle cerebral arteries. This was followed by reperfusion under anesthesia with isoflurane. The day after surgery, the eyes were treated three times (eye drop) or one time (oral administration) daily with KIOM-2015E for five days. Retinal histology was assessed in flat mounts and vertical sections to determine the effect of KIOM-2015E on I/R injury. Results: A significant loss of brain-specific homeobox/POU domain protein 3A (Brn3a) and neuron-specific class III beta-tubulin (Tuj-1) fluorescence and a marked increase in glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) expression were observed after five days in the PBS-treated MCAO group compared to the sham-operated control group. However, KIOM-2015E treatment reduced (1) MCAO-induced upregulation of GFAP and GS, (2) retinal ganglion cell loss, (3) nerve fiber degeneration, and (4) the number of TUNEL-positive cells. KIOM-2015E application also increased staining for parvalbumin (a marker of horizontal cell associated calcium-binding protein and amacrine cells) and recoverin (a marker of photoreceptor expression) in rats subjected to MCAO-induced retinal damage. Conclusions: Our findings indicated that KIOM-2015E treatment exerted protective effects against retinal damage following MCAO injury and that this extract may aid in the development of novel therapeutic strategies for retinal diseases, such as glaucoma and age-related macular disease.

The Protective Effects of Acer okamotoanum and Isoquercitrin on Obesity and Amyloidosis in a Mouse Model.

Obesity increases risk of Alzheimer's Disease (AD). A high fat diet (HFD) can lead to amyloidosis and amyloid beta (Aß) accumulation, which are hallmarks of AD. In this study, protective effects of the ethyl acetate fraction of Acer okamotoanum (EAO) and isoquercitrin were evaluated on obesity and amyloidosis in the HFD- and Aß-induced mouse model. To induce obesity and AD by HFD and Aß, mice were provided with HFD for 10 weeks and were intracerebroventricularly injected with Aß25-35. For four weeks, 100 and 10 mg/kg/day of EAO and isoquercitrin, respectively, were administered orally. Administration of EAO and isoquercitrin significantly decreased body weight in HFD and Aß-injected mice. Additionally, EAO- and isoquercitrin-administered groups attenuated abnormal adipokines release via a decrease in leptin and an increase in adiponectin levels compared with the control group. Furthermore, HFD and Aß-injected mice had damaged liver tissues, but EAO- and isoquercitrin-administered groups attenuated liver damage. Moreover, administration of EAO and isoquercitrin groups down-regulated amyloidosis-related proteins in the brain such as ß-secretase, presenilin (PS)-1 and PS-2 compared with HFD and Aß-injected mice. This study indicated that EAO and isoquercitrin attenuated HFD and Aß-induced obesity and amyloidosis, suggesting that they could be effective in preventing and treating both obesity and AD.

Cytoprotective effects of a proprietary red maple leaf extract and its major polyphenol, ginnalin A, against hydrogen peroxide and methylglyoxal induced oxidative stress in human keratinocytes.

Phytochemicals from functional foods are common ingredients in dietary supplements and cosmetic products for anti-skin aging effects due to their antioxidant activities. A proprietary red maple (Acer rubrum) leaf extract (Maplifa™) and its major phenolic compound, ginnalin A (GA), have been reported to show antioxidant, anti-melanogenesis, and anti-glycation effects but their protective effects against oxidative stress in human skin cells remain unknown. Herein, we investigated the cytoprotective effects of Maplifa™ and GA against hydrogen peroxide (H2O2) and methylglyoxal (MGO)-induced oxidative stress in human keratinocytes (HaCaT cells). H2O2 and MGO (both at 400 µM) induced toxicity in HaCaT cells and reduced their viability to 59.2 and 61.6%, respectively. Treatment of Maplifa™ (50 µg mL-1) and GA (50 µM) increased the viability of H2O2- and MGO-treated cells by 22.0 and 15.5%, respectively. Maplifa™ and GA also showed cytoprotective effects by reducing H2O2-induced apoptosis in HaCaT cells by 8.0 and 7.2%, respectively. The anti-apoptotic effect of Maplifa™ was further supported by the decreased levels of apoptosis associated enzymes including caspases-3/7 and -8 in HaCaT cells by 49.5 and 19.0%, respectively. In addition, Maplifa™ (50 µg mL-1) and GA (50 µM) reduced H2O2- and MGO-induced reactive oxygen species (ROS) by 84.1 and 56.8%, respectively. Furthermore, flow cytometry analysis showed that Maplifa™ and GA reduced MGO-induced total cellular ROS production while increasing mitochondria-derived ROS production in HaCaT cells. The cytoprotective effects of Maplifa™ and GA in human keratinocytes support their potential utilization for cosmetic and/or dermatological applications.

Flavonoids from Acer okamotoanum Inhibit Adipocyte Differentiation and Promote Lipolysis in the 3T3-L1 Cells.

Flavonoids, quercitrin, isoquercitrin (IQ), and afzelin, were isolated from ethyl acetate fraction of Acer okamotoanum. We investigated anti-obesity effects and mechanisms of three flavonoids from A. okamotoanum in the differentiated 3T3-L1 cells. The differentiated 3T3-L1 cells increased triglyceride (TG) contents, compared with non-differentiated normal group. However, treatments of three flavonoids from A. okamotoanum decreased TG contents without cytotoxicity. In addition, they showed significant down-regulation of several adipogenic transcription factors, such as γ-cytidine-cytidine-adenosine-adenosine-thymidine/enhancer binding protein -α, -ß, and peroxisome proliferator-activated receptor-γ, compared with non-treated control group. Furthermore, treatment of the flavonoids inhibited expressions of lipogenesis-related proteins including fatty acid synthase, adipocyte protein 2, and glucose transporter 4. Moreover, IQ-treated group showed significant up-regulation of lipolysis-related proteins such as adipose triglyceride lipase and hormone-sensitive lipase. In addition, flavonoids significantly activated 5'-adenosine monophosphate-activated protein kinase (AMPK) compared to control group. In particular, IQ showed higher inhibition of TG accumulation by regulation of pathways related with both adipogenesis and lipolysis, than other flavonoids. The present results indicated that three flavonoids of A. okamotoanum showed anti-obesity activity by regulation of adipocyte differentiation, lipolysis, and AMPK signaling, suggesting as an anti-obesity functional agents.

Acer okamotoanum inhibits adipocyte differentiation by the regulation of adipogenesis and lipolysis in 3T3­L1 cells.

Acer okamotoanum is reported to have various antioxidant, anti­inflammatory and beneficial immune system effects. The anti­adipocyte differentiation effects and mechanisms of the ethyl acetate (EtOAc) fraction of an A. okamotoanum extraction was investigated in 3T3­L1 adipocyte cells. Treatment with differentiation inducers increased the level of triglycerides (TGs) in 3T3­L1 adipocyte cells compared with an untreated control. However, the EtOAc fraction of A. okamotoanum significantly decreased TGs. Treatment with 1, 2.5 and 5 µg/ml showed weak activity, but TG production was inhibited at 10 µg/ml compared with the control. In addition, A. okamotoanum caused a significant downregulation of proteins related to adipogenesis, such as γ­cytidine­cytidine­adenosine­adenosine­thymidine/enhancer binding protein­α, ­ß and peroxisome proliferator­activated receptor­Î³, compared with the untreated control. Furthermore, A. okamotoanum significantly upregulated lipolysis related protein, hormone­sensitive lipase and the phosphorylation of adenosine monophosphate­activated protein kinase (AMPK). Therefore, these results indicate that A. okamotoanum suppressed adipogenesis and increased lipolysis and the activation of AMPK, suggesting a protective role in adipocyte differentiation.

Barringtogenol C-type Triterpenoid Saponins from the Stem Bark of Norway Maple (Acer Platanoides).

Four new barringtogenol C-type triterpenoid saponins, namely acerplatanosides A - D (1: -4: ), along with 22 known compounds (5: -26: ), were isolated from the stem bark of Norway maple (Acer platanoides). Their structures were elucidated on the basis of comprehensive spectroscopic analyses and chemical hydrolysis. This is the first report of triterpenoid saponins isolated from Norway maple. Compounds 1, 3: , and 4: showed cytotoxicity against 4 human cancer cell lines with IC50 values ranging from 9.4 to 39.5 µM.

Inhibitory effect of Acer tegmentosum maxim extracts on P. gingivalis LPS-induced periodontitis.

OBJECTIVE: Periodontitis disease is a chronic inflammation, and the prevention or treatment of periodontal disease is important for improving oral health and averting systemic diseases.Acer tegmentosum Maxim (ATM) is a type of deciduous tree in Korea. ATM extracts have been traditionally used to treat various dieases. This study investigated the effects of ATM extract on mitigation of periodontitis in vitro and in vivo. DESIGN: The current study investigated whether extracts ofAcer tegmentosum Maxim (ATM) attenuated periodontitis induced by Porphyromonas gingivalis-derived lipopolysaccharide (LPS) in vitro and in vivo. We used a rat model of experimental periodontitis that received oral administration of 1 mg/kg P. gingivalis-derived LPS for 10 days. Periodontitis models was treated with two different dosages of ATM (30 or 100 mg/kg) during the same period of periodontal induction for histological analysis. RESULTS: The results indicated that aqueous ATM extracts effectively ameliorated ligature-induced periodontitis through of the antibacterial, anti-oxidative, and anti-inflammatory activities. CONCLUSION: These pre-clinical results suggest the need for further studies on the anti-periodontitis effect of ATM in humans. Thus, ATM could be used as a natural anti-periodontitis agent for the treatment of periodontitis.

Suppression of 6-Hydroxydopamine-Induced Oxidative Stress by Hyperoside Via Activation of Nrf2/HO-1 Signaling in Dopaminergic Neurons.

In our ongoing research to discover natural products with neuroprotective effects, hyperoside (quercetin 3-O-galactoside) was isolated from Acer tegmentosum, which has been used in Korean traditional medicine to treat liver-related disorders. Here, we demonstrated that hyperoside protects cultured dopaminergic neurons from death via reactive oxygen species (ROS)-dependent mechanisms, although other relevant mechanisms of hyperoside activity remain largely uncharacterized. For the first time, we investigated the neuroprotective effects of hyperoside on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in neurons, and the possible underlying mechanisms. Hyperoside significantly ameliorated the loss of neuronal cell viability, lactate dehydrogenase release, excessive ROS accumulation and mitochondrial membrane potential dysfunction associated with 6-OHDA-induced neurotoxicity. Furthermore, hyperoside treatment activated the nuclear erythroid 2-related factor 2 (Nrf2), an upstream molecule of heme oxygenase-1 (HO-1). Hyperoside also induced the expression of HO-1, an antioxidant response gene. Remarkably, we found that the neuroprotective effects of hyperoside were weakened by an Nrf2 small interfering RNA, which blocked the ability of hyperoside to inhibit neuronal death, indicating the vital role of HO-1. Overall, we show that hyperoside, via the induction of Nrf2-dependent HO-1 activation, suppresses neuronal death caused by 6-OHDA-induced oxidative stress. Moreover, Nrf2-dependent HO-1 signaling activation represents a potential preventive and therapeutic target in Parkinson's disease management.

Acer okamotoanum and isoquercitrin improve cognitive function via attenuation of oxidative stress in high fat diet- and amyloid beta-induced mice.

Obesity induced by high-fat diet (HFD) and accumulation of amyloid beta (Aß) are known as a risk factor of Alzheimer's disease. We previously identified isoquercitrin (IQ) as an active compound of Acer okamotoanum. In the present study, we investigated the protective effects of the active ethyl acetate (EtOAc) fraction from A. okamotoanum and IQ on HFD and Aß25-35-induced cognitive impairment mice. C57BL/6J mice were fed with HFD for 10 weeks and then Aß25-35 was injected intracerebroventricularly (i.c.v.). The EtOAc fraction of A. okamotoanum and IQ were administered orally for 4 weeks at 100 and 10 mg kg-1 day-1, respectively. Learning and memory functions were evaluated using behavioral tests including T-maze, object recognition and Morris water maze tests. The HFD and Aß25-35 injection significantly impaired cognitive and memory function. However, administration of A. okamotoanum and IQ improved spatial cognitive ability and object recognition ability in T-maze and novel object recognition tests. In addition, A. okamotoanum and IQ-administered groups showed enhanced learning and memory function compared with HFD and Aß25-35-induced cognitive impairment mice in the Morris water maze test. Furthermore, administration of A. okamotoanum and IQ attenuated oxidative stress in the brain via inhibition of reactive oxygen species production, lipid peroxidation, and nitric oxide formation. Therefore, we suggest that A. okamotoanum and IQ improve HFD- and Aß25-35-induced cognitive impairment by inhibition of oxidative stress, and A. okamotoanum and IQ might be potential candidates for prevention and treatment of obesity- and Aß-induced cognitive impairment.

Identification of a Novel Oligosaccharide in Maple Syrup as a Potential Alternative Saccharide for Diabetes Mellitus Patients.

The incidence of diabetes mellitus (DM) is increasing rapidly and is associated with changes in dietary habits. Although restrictions in the use of sweeteners may prevent the development of DM, this might reduce the quality of life of patients with DM. Therefore, there has been a great deal of research into alternative sweeteners. In the search for such sweeteners, we analyzed the carbohydrate content of maple syrup and identified a novel oligosaccharide composed of fructose and glucose, linked at the C-4 of glucose and the C-6 of fructose. This oligosaccharide inhibited the release of fructose from sucrose by invertase (IC50: 1.17 mmol/L) and the decomposition of maltose by α-(1-4) glucosidase (IC50: 1.72 mmol/L). In addition, when orally administered together with sucrose to rats with DM, the subsequent plasma glucose concentrations were significantly lower than if the rats had been administered sucrose alone, without having any effect on the insulin concentration. These findings suggest that this novel oligosaccharide might represent a useful alternative sweetener for inclusion in the diet of patients with DM and may also have therapeutic benefits.

Metabolite Profiling of Two Maple-Derived Products Using Dereplication Based on High-Performance Liquid Chromatography-Diode Array Detector-Electrospray Ionization-Time-of-Flight-Mass Spectrometry: Sugar Maple Bark and Bud Hot-Water Extracts.

Recent studies about hot-water extracts from sugar maple (Acer saccharum Marsh.) bark and buds demonstrated that they contain high amounts of phenolic structures that may be used as antioxidant food additives. However, the detailed chemical composition of these maple-derived extracts has yet to be determined. By performing high-performance liquid chromatography-diode array detector-high-resolution mass spectrometry (HPLC-DAD-HRMS)-based dereplication, we were able to spike and classify almost 100 metabolites in each hot-water extract. The sugar maple bark hot-water extract is rich in simple phenolic compounds and phenylpropanoid derivatives, while bud extract contains predominantly flavonoids, benzoic acids, and their complex derivatives (condensed and hydrolyzable tannins). Among those chemical structures, we tentatively identified 69 phenolic compounds potentially reported for the first time in the genus Acer. Considering the growing commercial demand in natural products, the phenolic fingerprints of sugar maple bark and bud hot-water extracts will help in promoting these two maple-derived products as new sources of bioactive compounds in the food, nutraceutical, and cosmetic industries.

Antiosteoporotic Effects of Acer palmatum Extract on Osteoclastogenesis and Osteoblastogenesis.

Osteoporosis is a systemic skeletal disease that causes bone weakness and fragility. Consuming bone-beneficial nutrients through diet can prevent and treat osteoporosis. Acer palmatum (Japanese maple) leaves are used to make tea, but there have been few reports of their health benefits, especially regarding bone homeostasis. In this study, we evaluated the effects of A. palmatum hot water extract (APE) on osteoclastogenesis and osteoblastogenesis in cultured cells. APE suppressed the number of tartrate-resistant acid phosphatase-positive multinucleated osteoclasts in RANKL induced RAW264.7 cells. Furthermore, APE facilitated Alkaline phosphatase activity and calcium deposition during osteoblast differentiation in MC3T3-E1 cells. High-performance liquid chromatography analysis was performed to investigate the effective components of APE, and four flavonoids orientin, isoorientin, vitexin, and isovitexin were identified with the LC-MS analysis. Treatment with fractionated APE suppressed osteoclastogenesis and facilitated osteoblastogenesis in cultured cells. These findings suggest that APE contains antiosteoporotic compounds; thus, APE might have health promoting effects that help prevent osteoporosis by inhibiting osteoclastogenesis and facilitating osteoblastogenesis.