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.

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.

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.

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.

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.

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.

The efficacy of blueberry and grape seed extract combination on triple therapy for Helicobacter pylori eradication: a randomised controlled trial.

Helicobacter pylori is a major risk factor for gastritis, gastric ulcers and gastric cancer. Traditional therapy with proton pump inhibitor and antibiotics is regarded as optimal for H. pylori eradication whereas, the eradication rate is unsatisfactory. Studies have reported that cranberry may inhibit H. pylori adhesion to the human gastric mucus but lack of other berry extracts have been evaluated in clinical study. Thus, a 9-week add-on randomised controlled trial was conducted to explore the impact of blueberry and grape seed extract (BGE) combinations traditional therapy for H. pylori eradication. In results, we found that there was no significant difference of eradication rate between the berry extract group and placebo group in the intention-to-treat analysis and in the per-protocol analysis (94.64% versus 84.62%, p = 0.085). Diarrhoea, constipation and epigastric pain were observed increasing during ingestion of the berry extract in some cases. In conclusion, this study indicated that no significant difference existed between the BGE extract group and placebo group in eradication rate under triple therapy.

Durability of Nucleos(t)ide Analogues Treatment in Patients With Chronic Hepatitis B.

Long-term nucleos(t)ide analogues (NUCs) treatment is usually required for patients with chronic hepatitis B (CHB). However, whether discontinuation of NUCs is possible in selected patients remains debated. The aim of this study was to assess the durability of NUCs and predictors of sustained response after cessation of NUCs.Ninety-three CHB patients (29 HBeAg-positive and 64 HBeAg-negative) from 2 medical centers in Taiwan with discontinuation of NUCs after a median of 3 years' treatment were retrospectively reviewed. Fifteen (51.7%) HBeAg-positive and 57 (89.1%) HBeAg-negative patients achieved APASL treatment endpoints. Virological relapse (VR) and clinical relapse (CR) were defined according to APASL guidelines.Achieving APASL endpoint was associated with longer median time to CR in HBeAg-positive patients, but not in HBeAg-negative cases. The cumulative 1-year VR and CR rates were 55.3% and 14.4% in HBeAg-positive patients, and 77.7% and 41.9% in HBeAg-negative patients, respectively. In HBeAg-negative patients, baseline HBV DNA >10 IU/mL was the only predictor of VR (hazard ratio [HR] = 2.277, P = 0.019) and CR (HR = 3.378, P = 0.014). HBsAg >200 IU/mL at the end of treatment (EOT) was associated with CR (HR = 3.573, P = 0.023) in patients developing VR. HBeAg-negative patients with low baseline viral loads and low HBsAg levels at EOT had minimal risk of CR after achieving APASL treatment endpoint (P = 0.016).The VR rate is high, but the risk of CR is low within 1 year with consolidation treatment after HBeAg seroconversion. Longer consolidation treatment to reduce the risk of VR should be considered in HBeAg-positive patients. As high risk of VR and CR, cessation of NUCs therapy could be considered only in selected HBeAg-negative patients.

Effects of hot-water extracts from Ganoderma lucidum residues and solid-state fermentation residues on prebiotic and immune-stimulatory activities in vitro and the powdered residues used as broiler feed additives in vivo.

BACKGROUND: Large amounts of Ganoderma lucidum (GL) commercial products are provided in the worldwide market such as powders, tea bags, or capsules as dietary supplements which contained triterpenoids and/or polysaccharides. Therefore, it was estimated that several thousand tons of GL residues (GLR) are produced and discarded. For recycling uses, the aim of this study was to evaluate the benefits of two hot-water extracts from GLR (HWP_GLR) and solid-state fermentation GLR inoculated with GL mycelia (HWP_GLRF) on the growths of Lactobacillus rhamnosus and Bifidobacterium longum. The RAW264.7 cells were used to investigate the effects of HWP_GLR and HWP_GLRF on nitric oxide productions, phagocytic activities against FITC-labeled E. coli, and to lower lipopolysaccharide (LPS)-binding capacities. The powders of GLR and GLRF were used as additives in the commercial feeds for feeding broiler chicks in vivo to evaluate the immune-stimulatory and prebiotic activities. RESULTS: HWP_GLR and HWP_GLRF with molecular size 5 to 8 kDa were showed to stimulate growths of L. rhamnosus and B. longum. It was found that in the presence of polymyxin B HWP_GLR and HWP_GLRF could stimulate nitric oxide productions, elevate phagocytic activities against FITC-labeled E. coli, and to lower lipopolysaccharide-binding capacities in RAW264.7 cells. The broiler chicks were selected for feedings in vivo. The 1-day-old chicks were fed commercial feeds for 1 week, and then were fed without or with 4 or 8 % of GLR and GLRF additives for 3 weeks. There was no significant weight difference among feeding groups. However, the phagocytosis and natural killer cytotoxicity in the peripheral bloods, and prebiotic activities of bifidobacteria in feces of GLR and/or GLRF groups were significantly different compared to the control (P < 0.05). CONCLUSIONS: The GLR, GLRF, and their hot-water extracts with beneficial activities could be processed as feed additives which could increase the waste-recycling.

Inhibitory activities of acteoside, isoacteoside, and its structural constituents against protein glycation in vitro.

BACKGROUND: Advanced glycation end products (AGE) are substances that can induce insulin resistance in adipocyte, hepatocyte and muscle cells. This resistance correlates highly with cardiovascular disease and diabetic complications. Acteoside (A), a phenylethanoid glycoside, is an active compound in several plants and traditional herbal medicines. Acteoside, its structural isomer, isoacteoside (I), and their constituents, caffeic acid (C) and 3,4-dihydroxyphenylethanol (D), were used in the study to investigate the inhibitory activity against AGE formations in vitro. RESULTS: AGE formations were detected by anti-(Nϵ-(carboxymethyl)lysine (anti-CML), using bovine serum albumin (BSA)/glucose (glc) and BSA/galactose (gal) as models, or by anti-argpyrimidine (anti-AP), using BSA/methylglyoxal (MGO) as models. It was found that A, I, C, or D, each at 5 mM, could attenuate the CML formations detected by ELISA in the BSA/gal model of a 3-day or 5-day reaction, and showed significant differences (P < 0.01 or P < 0.001) compared to the control. However, these compounds showed a minor effect after a 7-day incubation. It was also found that C or D could lower the CML formations in the BSA/glc model and showed significant differences (P < 0.05 or P < 0.01) compared to the control after a 3-day, 5-day and 7-day reaction. It was found that A, I, C, or D, each at 0.5 mM or 5 mM, could attenuate the AP formations in the BSA/MGO model of a 3-day reaction and showed significant differences (P < 0.001) compared to the control. CONCLUSIONS: The results suggest the potential anti-glycation activities of A and I in vitro may apply to cell models at higher glucose concentrations or to diabetic animal models, and need further investigation.

Antioxidant and semicarbazide-sensitive amine oxidase inhibitory activities of glucuronic acid hydroxamate.

The antioxidant and inhibitory activities of glucuronic acid (GluA) and its synthesized 1-methoxyl-6-glucuronic acid hydroxamate (GluA-NHOH) against semicarbazide-sensitive amine oxidase (SSAO) were investigated. The scavenging activities of GluA-NHOH against 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radicals (half-inhibition concentration [IC50], 152µM) and hydroxyl radicals (IC50, 70nM) were determined. The protective activities of GluA-NHOH against hydroxyl radical-mediated calf thymus DNA damage and peroxynitrite-mediated dihydrorhodamine oxidation were also investigated. GluA-NHOH, but not GluA, exhibited dose-dependent protective activities. GluA-NHOH, but not GluA, effectively inhibited bovine SSAO activities in a dose-dependent manner, and was further confirmed by AO activity stains on an acrylamide gel. GluA-NHOH showed mixed noncompetitive inhibition of bovine SSAO with respect to benzylamine (substrate) and benzylamine-SSAO (substrate-enzyme complex). The Vmax' and Km' values were reduced in the presence of GluA-NHOH (0.04mM).

Antioxidant and amine oxidase inhibitory activities of hydroxyurea.

Hydroxyurea (HU, NH(2)CONHOH), or hydroxycarbamide, is a hydroxamic acid derivative used as a drug for anti-neoplasm and sickle-cell disease. In this study, HU was found to have antioxidant activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals and dose-dependent inhibitory activities against monoamine oxidase (MAO)-A, MAO-B, and semicarbazide-sensitive amine oxidase (SSAO) as compared to controls of clorgyline, deprenyl, and semicarbazide respectively. HU showed mixed-type, competitive-type, and competitive-type inhibition, respectively, with respect to substrates of MAO-A, MAO-B, and SSAO with apparent inhibition constants (Ki) of 19.46, 5.38, and 1.84 microM.

Effects of different types of yam (Dioscorea alata) products on the blood pressure of spontaneously hypertensive rats.

The aim of the present study was to investigate different yam treatments, including powdered-yam-products (PYP) and liquid-yam-products (LYP), with respect to spontaneously hypertensive rats (SHRs) blood pressure. PYP included alcohol-insoluble-solids of yam tuber, hot-air-drying (HAD) of yam tuber slices, steam-cooked once or twice followed by HAD which were subsequently powdered. LYP included water extracts of yam tuber (WEY) heated at 90 degrees C (WEY90H) or 95 degrees C for 10 min (WEY95H), and then stored at 4 degrees C for different numbers of day. PYP, WEY, and WEYH were found effectively to reduce the blood pressure of SHR and should be beneficial in food processing in the development of functional foods for blood pressure regulation.

Antioxidant and nitric oxide production inhibitory activities of galacturonyl hydroxamic acid.

The self-prepared pectin hydroxamic acid has been reported to have antioxidant activities [Yang, S. S., Cheng, K. D., Lin, Y. S., Liu, Y. W., & Hou, W. C. (2004). Pectin hydroxamic acids exhibit antioxidant activities in vitro. Journal of Agricultural and Food Chemistry, 52, 4270-4273]. In this study, the galacturonic acid (GalA), the monomer unit of the pectin polymer, was esterified with acidic methanol (1N HCl) at 4°C with gentle stirring for 5days to get galacturonic acid methyl ester which was further reacted with alkaline hydroxylamine to get galacturonyl hydroxamic acid (GalA-NHOH). The GalA-NHOH was used to test the antioxidant and antiradical activities in the comparison with GalA. The scavenging activities of GalA-NHOH against DPPH radicals (half-inhibition concentration, IC50, was 82µM), hydroxyl radicals detected by electron spin resonance (IC50 was 0.227nM in the comparison with Trolox of 0.433µM), superoxide radicals (IC50 was 830µM) were determined. The protection activities of GalA-NHOH against hydroxyl radicals-mediated calf thymus DNA damages, linoleic acid peroxidation and peroxynitrite-mediated dihydrorhodamine 123 oxidations were also investigated. It was found that the GalA-NHOH exhibited dose-dependently antioxidant activity and few or none was found in GalA. The GalA-NHOH was used to evaluate the suppressed activity of nitric oxide (NO) productions of RAW264.7 cells in the presence of lipopolysaccharide (LPS, 100ng/ml) as inducers. It was found that GalA-NHOH (0.02-0.1mg/ml) could dose-dependently suppress the NO productions (expressed as nitrite concentrations) in RAW264.7 cells without significant cytotoxicity.