Extracts and Scirpusin B from Recycled Seeds and Rinds of Passion Fruits (Passiflora edulis var. Tainung No. 1) Exhibit Improved Functions in Scopolamine-Induced Impaired-Memory ICR Mice.

In this paper, the seeds and rinds of passion fruit, which are the agricultural waste of juice processing, were recycled to investigate their biological activities for sustainable use. De-oiled seed powders (S) were successively extracted by refluxing 95% ethanol (95E), 50E, and hot water (HW), respectively, to obtain S-95EE, S-50EE, and S-HWE. Dried rind powders were successively extracted by refluxing HW and 95E to obtain rind-HWE and rind-95EE, respectively. S-50EE and S-95EE showed the most potent extracts, such as anti-amyloid-ß1-42 aggregations and anti-acetylcholinesterase inhibitors, and they exhibited neuroprotective activities against amyloid-ß25-35-treated or H2O2-treated SH-SY5Y cells. Scirpusin B and piceatannol were identified in S-95EE, S-50EE, and rind-HWE, and they showed anti-acetylcholinesterase activity at 50% inhibitory concentrations of 62.9 and 258.9 µM, respectively. Daily pretreatments of de-oiled seed powders and rind-HWE (600 mg/kg), S-95EE, and S-50EE (250 mg/kg) or scirpusin B (40 mg/kg) for 7 days resulted in improved learning behavior in passive avoidance tests and had significant differences (p < 0.05) compared with those of the control in scopolamine-induced ICR mice. The seeds and rinds of passion fruit will be recycled as materials for the development of functional foods, promoting neuroprotection and delaying the onset of cognitive dysfunctions.

Vitisin B, a resveratrol tetramer from Vitis thunbergii var. taiwaniana, ameliorates impaired glucose regulations in nicotinamide/streptozotocin-induced type 2 diabetic mice.

Background and aim: In Taiwan, Vitis thunbergii var. taiwaniana (VTT) is used in traditional medicine and as a local tea. VTT rich in resveratrol and resveratrol oligomers have been reported to exhibit anti-obesity and anti-hypertensive activities in animal models; however, no studies have investigated type 2 diabetes mellitus (T2DM) treatments. This study aimed to investigate the anti-T2DM effects of resveratrol tetramers isolated from the VTT in nicotinamide/streptozotocin (STZ)-induced Institute of Cancer Research (ICR) mice. Experimental procedure: The oral glucose tolerance test (OGTT) was used to imitate postprandial blood glucose (BG) regulations in mice by pre-treatment with VTT extracts, resveratrol tetramers of vitisin A, vitisin B, and hopeaphenol 30 min before glucose loads. Vitisin B (50 mg/kg) was administered to treat T2DM-ICR mice once daily for 28 days to investigate its hypoglycemic activity. Results and conclusion: Mice pre-treated with VTT-S-95EE, or vitisin B (100 mg/kg) 30-min before glucose loading showed significant reductions (P < 0.001) in the area under the curve at 120-min (BG-AUC0-120) than those without pre-treatment with VTT-S-95 E E or vitisin B. Vitisin B-treated T2DM mice showed hypoglycemic activities via a reduction in plasma dipeptidyl peptidase (DPP)-IV activities to maintain insulin actions and differed significantly than those of untreated T2DM mice (P < 0.05), and also reduced BG-AUC0-120 and insulin-AUC0-120 in the OGTT.These in vivo results showed that VTT containing vitisin B would be beneficial for developing nutraceuticals and/or functional foods for glycemic control in patients with T2DM, which should be investigated further.

Inhibition of Acetylcholinesterase and Amyloid-ß Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment.

Currently, no drug is effective in delaying the cognitive impairment of Alzheimer's disease, which ranks as one of the top 10 causes of death worldwide. Hydroxylated stilbenes are active compounds that exist in fruit and herbal plants. Piceatannol (PIC) and gnetol (GNT), which have one extra hydroxyl group in comparison to resveratrol (RSV), and rhapontigenin (RHA) and isorhapontigenin (isoRHA), which were metabolized from PIC in vivo and contain the same number of hydroxyl groups as RSV, were evaluated for their effects on Alzheimer's disease-associated factors in vitro and in animal experiments. Among the five hydroxylated stilbenes, PIC was shown to be the most active in DPPH radical scavenging and in inhibitory activities against acetylcholinesterase and amyloid-ß peptide aggregations, with concentrations for half-maximal inhibitions of 40.2, 271.74, and 0.48 µM. The different interactions of the five hydroxylated stilbenes with acetylcholinesterase or amyloid-ß were obtained by molecular docking. The scopolamine-induced ICR mice fed with PIC (50 mg/kg) showed an improved learning behavior in the passive avoidance tests and had significant differences (p < 0.05) compared with those in the control group. The RHA and isoRHA at 10 µM were proven to stimulate neurite outgrowths in the SH-SY5Y cell models. These results reveal that nutraceuticals or functional foods containing PIC have the potential for use in the treatment of neurodegenerative disorders.

Anti-adipogenic activities of pheophorbide a and pyropheophorbide a isolated from wild bitter gourd (Momordica charantia L. var. abbreviata Seringe) in vitro.

BACKGROUND: The wild bitter gourd (WBG) is a commonly consumed vegetable in Asia that has antioxidant and hypoglycemic properties. The present study aimed to investigate the anti-adipogenic activities of isolated compounds from WBG on 8-day differentiated cultures of 3 T3-L1 adipocytes that were then stained with Oil Red O (ORO) or diamidino-2-phenylindole (DAPI). RESULTS: ORO stains of the methanol extracts of de-seeded HM86 cultivar of WBG (WBG-M) and the ethyl acetate fractions (WBG-M-EA) showed anti-adipogenic activities against differentiated adipocytes. Two chlorophyll-degraded compounds, pheophorbide a (1) and pyropheophorbide a (2), were isolated from WBG-M-EA. Treatments with 1 (5, 10, and 20 µmol L-1 ) and 2 (2.5, 5, and 10 µmol L-1 ) showed dose-dependent reductions in lipid accumulations and reduced nuclear DAPI stains in differentiated 3 T3-L1 adipocytes. The concentrations for 50% inhibition against lipid accumulations of 1 and 2, respectively, were 16.05 and 7.04 µmol L-1 . Treatments with 1 and 2 showed enhanced lactate dehydrogenase release in the first 4-day cell mitotic clonal expansions during the differentiating cultural processes, although the effect was less on the non-differentiating cultural processes. Thus, 1 and 2 were more toxic to differentiating adipocytes than to non-differentiated pre-adipocytes, which partly resulted in anti-adipogenic activities with lowered lipid accumulations. CONCLUSION: Both 1 and 2 showed anti-adipogenic activities in cell models. These chlorophyll-degraded compounds commonly exist in several vegetables during storage or edible seaweeds, which will provide resources for further investigations aiming to test anti-obesity in animal studies. © 2022 Society of Chemical Industry.

Vitisin A, a Resveratrol Tetramer, Improves Scopolamine-Induced Impaired Learning and Memory Functions in Amnesiac ICR Mice.

Resveratrol has been reported to exhibit neuroprotective activities in vitro and in vivo. However, little is known about resveratrol tetramers of hopeaphenol, vitisin A, and vitisin B with the same molecular mass in the improvement of degenerative disorders. In this study, two 95% ethanol extracts (95EE) from stem parts of Vitis thunbergii Sieb. & Zucc. (VT-95EE) and from the root (R) parts of Vitis thunbergii var. taiwaniana (VTT-R-95EE) showed comparable acetylcholinesterase (AChE) inhibitory activities. It was found that VT-95EE and VTT-R-95EE showed different distribution patterns of identified resveratrol and resveratrol tetramers of hopeaphenol, vitisin A, and vitisin B based on the analyses of HPLC chromatographic profiles. The hopeaphenol, vitisin A, and vitisin B, showed AChE and monoamine oxidase-B inhibitions in a dose-dependent manner, among which vitisin B and vitisin A exhibited much better activities than those of resveratrol, and had neuroprotective activities against methylglyoxal-induced SH-SY5Y cell deaths. The scopolamine-induced amnesiac ICR mice treated with VT-95EE and its ethyl acetate-partitioned fraction (VT-95EE-EA) at doses of 200 and 400 mg/kg, or vitisin A at a dose of 40 mg/kg, but not vitisin B (40 mg/kg), were shown significantly to improve the impaired learning behaviors by passive avoidance tests compared to those in the control without drug treatments (p < 0.05). Compared to mice in the control group, the brain extracts in the vitisin A-treated mice or donepezil-treated mice showed significant reductions in AChE activities and malondialdehyde levels (p < 0.05), and elevated the reduced protein expressions of brain-derived neurotrophic factor (BDNF) and BDNF receptor, tropomyosin receptor kinase B (TrkB). These results revealed that vitisin A was the active constituent in the VT-95EE and VTT-95EE, and the VT medicinal plant and that the endemic variety of VTT has potential in developing functional foods for an unmet medical need for neurodegenerative disorders.

Hydrolysable Tannins Exhibit Acetylcholinesterase Inhibitory and Anti-Glycation Activities In Vitro and Learning and Memory Function Improvements in Scopolamine-Induced Amnesiac Mice.

Agricultural waste from the hulls of water caltrop (Trapa taiwanesis Nakai, TT-hull) was extracted by either steeping them in cold 95% ethanol (C95E), refluxing 95E, refluxing 50E, or refluxing hot water (HW) to obtain C95EE, 95EE, 50EE, and HWE, respectively. These four extracts showed acetylcholinesterase (AChE) inhibitory activities and free radical scavenging activities, as well as anti-non-enzymatic protein glycation in vitro. Eight compounds were isolated from TT-hull-50EE and were used to plot the chromatographic fingerprints of the TT-hull extracts, among which tellimagrandin-I, tellimagrandin-II, and 1,2,3,6-tetra-galloylglucose showed the strongest AChE inhibitory activities, and they also exhibited anti-amyloid ß peptide aggregations. The scopolamine-induced amnesiac ICR mice that were fed with TT-hull-50EE or TT-hull-HWE (100 and 200 mg/kg) or tellimagrandin-II (100 and 200 mg/kg) showed improved learning behavior when evaluated using passive avoidance or water maze evaluation, and they showed significant differences (p < 0.05) compared to those in the control group. The enriched hydrolysable tannins of the recycled TT-hull may be developed as functional foods for the treatment of degenerative disorders.

Reductions of copper ion-mediated low-density lipoprotein (LDL) oxidations of trypsin inhibitors, the sweet potato root major proteins, and LDL binding capacities.

BACKGROUND: The root major proteins of sweet potato trypsin inhibitors (SPTIs) or named sporamin, estimated for 60 to 80% water-soluble proteins, exhibited many biological activities. The human low-density lipoprotein (LDL) showed to form in vivo complex with endogenous oxidized alpha-1-antitrypsin. Little is known concerning the interactions between SPTIs and LDL in vitro. RESULTS: The thiobarbituric-acid-reactive-substance (TBARS) assays were used to monitor 0.1 mM Cu2+-mediated low-density lipoprotein (LDL) oxidations during 24-h reactions with or without SPTIs additions. The protein stains in native PAGE gels were used to identify the bindings between native or reduced forms of SPTIs or soybean TIs and LDL, or oxidized LDL (oxLDL). It was found that the SPTIs additions showed to reduce LDL oxidations in the first 6-h and then gradually decreased the capacities of anti-LDL oxidations. The protein stains in native PAGE gels showed more intense LDL bands in the presence of SPTIs, and 0.5-h and 1-h reached the highest one. The SPTIs also bound to the oxLDL, and low pH condition (pH 2.0) might break the interactions revealed by HPLC. The LDL or oxLDL adsorbed onto self-prepared SPTIs-affinity column and some components were eluted by 0.2 M KCl (pH 2.0). The native or reduced SPTIs or soybean TIs showed different binding capacities toward LDL and oxLDL in vitro. CONCLUSION: The SPTIs might be useful in developing functional foods as antioxidant and nutrient supplements, and the physiological roles of SPTIs-LDL and SPTIs-oxLDL complex in vivo will investigate further using animal models.

Correction to: Anti-glycation, anti-hemolysis, and ORAC activities of demethylcurcumin and tetrahydroxycurcumin in vitro and reductions of oxidative stress in D-galactose-induced BALB/c mice in vivo.

In the publication of this article (Liu et al. 2019), there was an error in the method and ethics declarations sections which were published with incorrect animal experiment approval number. The error: 'These animal experimental protocols have been reviewed and approved by the Institutional Animal Care and Use Committee of Taipei Medical University (LAC-99-0142).' Should instead read: These animal experimental protocols have been reviewed and approved by the Institutional Animal Care and Use Committee of Taipei Medical University (LAC-2016-0340).

Acetylcholinesterase inhibitory activity and neuroprotection in vitro, molecular docking, and improved learning and memory functions of demethylcurcumin in scopolamine-induced amnesia ICR mice.

In this study, demethylcurcumin (DC), a minor constituent in curcuminoids, showed better anti-acetylcholinesterase (anti-AChE) activities, anti-amyloid ß peptide aggregation, neuroprotective activities in 6-hydroxydopamine-treated SH-SY5Y cell models, and anti-nitric oxide production in lipopolysaccharide-treated RAW 264.7 macrophages than those of curcumin. Based on molecular docking analyses with AChE, the meta-hydroxyl group in DC, nonexistent in curcumin, showed the formation of hydrogen bonds with Ser293 and Tyr341 in the binding sites of AChE. For animal experiments, scopolamine-induced amnesia ICR mice were used to analyze the learning and memory functions of DC in comparison with the positive control donepezil. Mice fed with DC (50 mg kg-1) or donepezil (5 mg kg-1) showed improvement and a significant difference compared to those in the control group (P < 0.05, 0.01, or 0.001) in a passive avoidance test and in a water maze probe test. The brain extracts of the mice in the DC or donepezil group showed reduced AChE activities and higher ORAC activities and also showed a significant difference compared to those in the control group (P < 0.05, 0.01, or 0.001). DC might be beneficial for developing functional foods or as a lead compound for the treatment of degenerative disorders.

In vitro and in vivo evaluation of the neuroprotective activity of Uncaria hirsuta Haviland.

The incidence of neurodegeneration leading to the conditions such as Alzheimer's and Parkinson's diseases are on the increase, they require the approaches that focus on protection prevention rather than treatment. Plants are rich sources of many compounds which possess medicinal properties. We sought to investigate the neuroprotective effects of Uncariahirsuta and its compounds on d-galactose-induced stress in BALB/c mice as well as 6-hydroxydopamine (6-OHDA)-induced stress in mouse nerve growth factor (mNGF)-differentiated PC12 cells. Our results demonstrate that the 95% ethanol extract of U. hirsuta reversed the d-galactose-induced learning and memory dysfunctions and decreased the malodialdehyde levels. Furthermore, the isolated compounds, 5ß-carboxystrictosidine (1) and chlorogenic acid (2), protected mNGF-differentiated PC12 cells against toxicity induced by 6-OHDA by acting as antiapoptotic agents. The 50% inhibitory concentration (IC50) for intracellular reactive oxygen species (ROS) scavenging was found to be 24.5 (for 1) and 19.7 µM (for 2), and both 1 and 2 reduced intracellular calcium levels with respective IC50 values of 46.9 and 27 µM. Interestingly, both compounds inhibited caspase 3 and 9 activities with respective IC50 values of 25.6 and 24.5 µM for 1 and 19.4 and 16.3 µM for 2. Our results identify U. hirsuta and its active compounds as potential neuroprotective agents and deserve further evaluation for drug development for neuroprotection in the future.

Anti-glycation, anti-hemolysis, and ORAC activities of demethylcurcumin and tetrahydroxycurcumin in vitro and reductions of oxidative stress in D-galactose-induced BALB/c mice in vivo.

BACKGROUND: There were few report concerning anti-glycation and antioxidant activities of the minor amounts of components in curcuminoids, demethylcurcumin and tetrahydroxycurcumin, in vitro and in vivo. RESULTS: The bovine serum albumin/galactose of non-enzymatic glycation models, radical-induced hemolysis, and oxygen radical absorbance capacity (ORAC) were studied in vitro, and the D-galactose-induced oxidative stress in BALB/c mice and then demethylcurcumin or tetrahydroxycurcumin interventions in vivo. The parameters of oxidative stress in plasma and brain extracts were determined among animal groups with or without both curcuminoids interventions. The demethylcurcumin and tetrahydroxycurcumin exhibited anti-glycation, anti-hemolysis, and ORAC activities, and showed much better and significant difference (P < 0.05) compared to those of curcumin in vitro. In animal experiments, the intervened two curcuminoids at both concentrations showed to lower serum malondialdehyde (MDA), brain MDA levels and iNOS protein expressions, and elevate serum ORAC activities, and showed difference (P < 0.05) compared to the galactose-induced control. CONCLUSION: The demethylcurcumin and tetrahydroxycurcumin showed potentials in developing functional foods for antioxidant-related purposes.

Design of Diarylheptanoid Derivatives as Dual Inhibitors Against Class IIa Histone Deacetylase and ß-amyloid Aggregation.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple etiologies. Beta-amyloid (Aß) self-aggregation and overexpression of class IIa histone deacetylases (HDACs) are strongly implicated with AD pathogenesis. In this study, a series of novel diarylheptanoid derivatives were designed, synthesized and evaluated for use as dual Aß self-aggregation and class IIa HDAC inhibitors. Among these compounds, 4j, 5c, and 5e displayed effective inhibitions for Aß self-aggregation, HDAC5 activity and HDAC7 activity with IC50 values of <10 µM. The compounds contain three common features: (1) a catechol or pyrogallol moiety, (2) a carbonyl linker and (3) an aromatic ring that can function as an HDAC cap and create hydrophobic interactions with Aß1-42. Furthermore, compounds 4j, 5c, and 5e showed no significant cytotoxicity to human neuroblastoma SH-SY5Y cells and also exhibited neuroprotective effect against H2O2-induced toxicity. Overall, these promising in vitro data highlighted compounds 4j, 5c, and 5e as lead compounds that are worthy for further investigation.

135-Day Interventions of Yam Dioscorin and the Dipeptide Asn-Trp (NW) To Reduce Weight Gains and Improve Impaired Glucose Tolerances in High-Fat Diet-Induced C57BL/6 Mice.

The C57BL/6J mice were fed a 135-day normal diet or a high-fat diet (HFD) without, or concurrent with, a single yam dioscorin (80 mg/kg) or dipeptide NW (40 mg/kg) intervention every day. The final body weights (g) of mice were 26.1 ± 1.4, 34.97 ± 2.1, 31.75 ± 2.6, and 31.66 ± 3.1, respectively, for normal diet-fed, HFD-fed, dioscorin-intervened, and NW-intervened group. The mice in both intervened groups showed similar less weight gains and had significant differences (P < 0.05) compared to those in the HFD group under the same cumulative HFD intakes. The blood biochemical index of mice with dioscorin interventions showed significantly lower contents in total cholesterol and low-density lipoprotein, and NW interventions showed significantly lower total triglyceride contents compared to those of the HFD group (P < 0.05). Both intervened mice exhibited similar reductions in total visceral lipid contents and have significant differences compared to those of the HFD group (P < 0.05). The dioscorin intervention was better than NW interventions in lowering blood glucose levels by oral glucose tolerance tests and both showed significant differences (P < 0.05) compared to those in the HFD group. Yam dioscorin or dipeptide NW will potentially be used for preventive functional foods of less body weight gains and impaired glucose tolerance controls, which require further clinical trial investigations.

Antiglycation, radical scavenging, and semicarbazide-sensitive amine oxidase inhibitory activities of acetohydroxamic acid in vitro.

Advanced glycation endproducts (AGEs) can promote intracellular reactive oxygen species production, and the levels of AGEs are highly correlated with cardiovascular disease and diabetes complications. Acetohydroxamic acid (acetH) is a bacterial urease inhibitor drug used to treat kidney stones and infections in the urinary tract, and hydroxyurea (HU) is a drug used for antineoplasm and sickle cell diseases. Both acetH and HU are hydroxamic acid derivatives. It was found that acetH and HU at 2.5 or 5 mM showed anti-AGE formation by lowering the AGEs' fluorescent intensities and Nε-(carboxymethyl)lysine formation in bovine serum albumin/galactose models, and both showed better and significant differences (P<0.05) compared to the positive control of aminoguanidine. Regarding radical scavenging activities, the half-inhibition concentrations (IC50) of acetH against α,α-diphenyl-ß-picrylhydrazyl radical and hydroxyl radical were 34.86 and 104.42 µM, respectively. The IC50 of acetH against semicarbazide-sensitive amine oxidase was 10.56 µM, and acetH showed noncompetitive inhibition respective to the substrates (benzylamine). The antiglycation, antioxidant, and semicarbazide-sensitive amine oxidase inhibitory activities of acetH prove that it has the potential for treating cardiovascular disease and diabetes complications and it needs further investigation in animal models.

Hot-Water Extracts from Roots of Vitis thunbergii var. taiwaniana and Identified ε-Viniferin Improve Obesity in High-Fat Diet-Induced Mice.

In this study, hot-water extracts (HW) from roots of Vitis thunbergii var. taiwaniana (VTT-R) were shown to lower levels of lipid accumulation significantly (P < 0.01 or 0.001) compared to the control in 3T3-L1 adipocytes. The VTT-R-HW (40 mg/kg) interventions concurrent with a high-fat (HF) diet in C57BL/6 mice over a 5 eek period were shown to reduce body weights significantly (P < 0.05) compared to those of mice fed a HF diet under the same food-intake regimen. The (+)-ε-viniferin isolated from VTT-R-HW was shown to reduce the size of lipid deposits significantly compared to the control (P < 0.05 or 0.001) in 3T3-L1 adipocytes, and dose-dependent 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitions showed that the 50% inhibitory concentration was calculated to be 96 µM. The two-stage (+)-ε-viniferin interventions (10 mg/kg, day 1 to day 38; 25 mg/kg, day 39 to day 58) were shown to lower mice body weights significantly (P < 0.05 or 0.001), the weight ratio of mesenteric fat, blood glucose, total cholesterol, and low-density lipoprotein compared to that of the HF group under the same food-intake regimen but without concurrent VTT-R-HW interventions. It might be possible to use VTT-R-HW or (+)-ε-viniferin as an ingredient in the development of functional foods for weight management, and this will need to be investigated further.

Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P < 0.05 or 0.001). These results suggested that RRDY and yam dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models.

Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer's disease.

Neprilysin (NEP) is the most important Aß-degrading enzyme. Its expression level decreases with age and inversely correlated with amyloid accumulation, suggesting its correlation with the late-onset of Alzheimer's disease. Recently, many reports showed that upregulating NEP level is a promising strategy in the prevention and therapy of Alzheimer's disease. Here, we used a sensitive fluorescence-based Aß digestion assay to screen 25 curcumin analogs for their ability to upregulate NEP activity. To our surprise, four compounds, dihydroxylated curcumin, monohydroxylated demethoxycurcumin, and mono- and di-hydroxylated bisdemethoxycurcumin, increased NEP activity, while curcumin did not. The ability of these polyhydroxycurcuminoids to upregulate NEP was further confirmed by mRNA and protein expression levels in the cell and mouse models. Finally, feeding monohydroxylated demethoxycurcumin (also named demethylcurcumin) or dihydroxylated bisdemethoxycurcumin (also named bisdemethylcurcumin) to APPswe/PS1dE9 double transgenic mice upregulated NEP levels in the brain and reduced Aß accumulation in the hippocampus and cortex. These polyhydroxycurcuminoids offer hope in the prevention of Alzheimer's disease.

Protective Effects of Minor Components of Curcuminoids on Hydrogen Peroxide-Treated Human HaCaT Keratinocytes.

Hydrogen peroxide, one of the reactive oxygen species (ROS), can cause intracellular oxidative stress associated with skin aging and/or photoaging. Curcumin, a polyphenol in turmeric, has been reported to exhibit biological activity. In this study, five naturally occurring curcuminoids [curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), monohydroxy-DMC, and monohydroxy-BDMC] were used to investigate their protective roles against hydrogen peroxide-induced oxidative stress in the immortalized human keratinocyte cell lines (HaCaT cells). These five curcuminoids at 10 µM, but not at 5 µM, were shown to exhibit cytotoxicities toward HaCaT keratinocytes. Therefore, a 5 µM concentration of the five curcuminoids was selected for further investigations. Cells were pretreated with or without curcuminoids for 2.5 h before 24-h hydrogen peroxide (150 µM) treatments. Pretreatments with the minor components monohydroxy-DMC or monohydroxy-BDMC, but not curcumin, DMC, and BDMC, showed protective activity, elevating cell viability compared to cells with direct hydrogen peroxide treatments. Pretreatments with monohydroxy-DMC and monohydroxy-BDMC showed the best protective effects, reducing apoptotic cell populations and intracellular ROS, as demonstrated by flow cytometry, as well as reducing the changes of the mitochondrial membrane potential compared to cells with direct hydrogen peroxide treatments. The pretreatments with monohydroxy-DMC and monohydroxy-BDMC reduced c-jun and c-fos mRNA expression and p53 tumor suppressor protein expression and increased HO-1 protein expression and glutathione peroxidase (GPx) activity, respectively, compared to cells with direct hydrogen peroxide treatments. The five curcuminoids exhibited similar hydrogen peroxide-scavenging activity in vitro. It was proposed that monohydroxy-DMC and monohydroxy-BDMC could induce antioxidant defense systems better than curcumin, DMC, or BDMC could against hydrogen peroxide-induced oxidative stress and apoptosis of HaCaT keratinocytes and that they may have potential as ingredients in antiaging cosmetics for skin care.

Vitis thunbergii var. taiwaniana Extracts and Purified Compounds Ameliorate Obesity in High-Fat Diet-Induced Obese Mice.

The increasing prevalence of obesity continues to gain more attention worldwide. In this study, diet-induced obese mice were used to evaluate the antiobesity effects of extracts, fractions, and purified compounds from Vitis thunbergii var. taiwaniana (VTT). The C57BL/6J mice were fed a 5-week high-fat diet (HF) concurrently with ethanol extracts (Et-ext, 80 mg/kg) from roots (R), stems (S), and leaves (L) by oral gavage daily. Only R-Et-ext interventions showed significant weight reduction in mice compared with those in the HF group; however, mouse plasma contents of total cholesterols (TC), total triglycerides (TG) and low-density lipoproteins (LDL) of all three Et-ext intervened groups showed significant reductions compared with those in the HF group. Furthermore, intervention with the ethyl acetate-partitioned fraction (EA-fra, 60 mg/kg) from R-Et-ext but not the n-butanol-partitioned fraction or water fraction from R-Et-ext showed significant weight reduction in mice compared with those in the HF group. The same molecular weights of three resveratrol tetramers, (+)-hopeaphenol, (+)-vitisin A, and (-)-vitisin B, were isolated from the EA-fra of VTT-R. The (+)-vitisin A and fenofibrate (25 mg/kg) but not the (+)-hopeaphenol and (-)-vitisin B interventions showed significant weight reduction in mice compared with those in the HF group. The total feed intake among the HF groups with or without interventions showed no significant differences. The mouse plasma contents of TC, TG, LDL, free fatty acid, and plasma lipase activity of the three resveratrol tetramer-intervened groups showed reductions in the mice compared with those in the HF group. It was proposed that the lipase inhibitory activities of VTT extracts and purified resveratrol tetramers might contribute in part to the antiobesity effect, and these results suggested that VTT may be developed as functional food for achieving antiobesity objectives and requires further investigation.

Anti-α-glucosidase and Anti-dipeptidyl Peptidase-IV Activities of Extracts and Purified Compounds from Vitis thunbergii var. taiwaniana.

Ethanol extracts (Et) from the stem (S) and leaf (L) of Vitis thunbergii var. taiwaniana (VTT) were used to investigate yeast α-glucosidase and porcine kidney dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Both VTT-Et showed complete α-glucosidase inhibition at 0.1 mg/mL; VTT-S-Et and VTT-L-Et showed 26 and 11% DPP-IV inhibition, respectively, at 0.5 mg/mL. The VTT-Et interventions (20 and 50 mg/kg) resulted in improvements in impaired glucose tolerance of diet-induced obese rats. (+)-Hopeaphenol, (+)-vitisin A, and (-)-vitisin B were isolated from the ethyl acetate fractions of S-Et and showed yeast α-glucosidase inhibition (IC50 = 18.30, 1.22, and 1.02 µM) and porcine kidney DPP-IV inhibition (IC50 = 401, 90.75, and 15.3 µM) compared to acarbose (6.39 mM) and sitagliptin (47.35 nM), respectively. Both (+)-vitisin A and (-)-vitisin B showed mixed noncompetitive inhibition against yeast α-glucosidase and porcine kidney DPP-IV, respectively. These results proposed that VTT extracts might through inhibitions against α-glucosidase and DPP-IV improve the impaired glucose tolerance in diet-induced obese rats.