scholarly journals Mulberry Fruit Prevents Diabetes and Diabetic Dementia by Regulation of Blood Glucose through Upregulation of Antioxidative Activities and CREB/BDNF Pathway in Alloxan-Induced Diabetic Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
A Young Min ◽  
Jae-Myung Yoo ◽  
Dai-Eun Sok ◽  
Mee Ree Kim
Keyword(s):  
Ethanolic Extract ◽  
Ethyl Acetate Fraction ◽  
Diabetic Mice ◽  
Neuroprotective Effects ◽  
Memory Impairments ◽  
Beneficial Effects ◽  
Body Weight Reduction ◽  
Mulberry Fruit ◽  
Pathway Activation ◽  
Bdnf Pathway

Although mulberry fruit has various beneficial effects, its effect on diabetes-related dementia remains unknown. We investigated whether the ethyl acetate fraction of ethanolic extract of mulberry fruit (MFE) could alleviate biochemical and behavioral deficits in alloxan-induced diabetic mice. In the diabetic mice, MFE considerably abolished multiple deficits, e.g., body weight reduction; water and food intake increase; and hyperglycemia, hyperlipidemia, hypoinsulinism, and hypertrophy of the liver, kidneys, spleen, and brain. A 200 mg/kg MFE dose reduced malondialdehyde levels and improved antioxidant enzyme activity in the liver, kidney, and brain tissues. MFE attenuated hyperglycemia-induced memory impairments and acetylcholine deprivation, protected neuronal cells in CA1 and CA3 regions via p-CREB/BDNF pathway activation, and reduced amyloid-β precursor protein and p-Tau expressions in the brain tissue. In conclusion, MFE exerts antidiabetic and neuroprotective effects by upregulating antioxidative activities and p-CREB/BDNF pathway in chronic diabetes. Therefore, MFE may be used as a therapeutic agent for diabetes and diabetic neurodegenerative diseases.

scholarly journals Neuroprotective Effects of Euonymus alatus Extract on Scopolamine-Induced Memory Deficits in Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 449 ◽  
Author(s):  
Yunju Woo ◽  
Ji Sun Lim ◽  
Jisun Oh ◽  
Jeong Soon Lee ◽  
Jong-Sang Kim
Keyword(s):  
Antioxidant Enzyme ◽  
Neurotrophic Factor ◽  
Ethanolic Extract ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Leaf Extracts ◽  
Behavioral Impairment ◽  
Neuroprotective Effects ◽  
Euonymus Alatus ◽  
Beneficial Effects

Euonymus alatus is considered to elicit various beneficial effects against cancer, hyperglycemia, menstrual discomfort, diabetic complications, and detoxification. The young leaves of this plant are exploited as food and also utilized for traditional medicine in East Asian countries, including Korea and China. Our preliminary study demonstrated that ethanolic extract from the Euonymus alatus leaf (EAE) exhibited the strongest antioxidant enzyme-inducing activity among more than 100 kinds of edible tree leaf extracts. This study investigated whether EAE could attenuate the cognitive deficits caused by oxidative stress in mice. Oral intubation of EAE at 100 mg/kg bw or higher resulted in significant improvements to the memory and behavioral impairment induced via i.p. injection of scopolamine. Furthermore, EAE enhanced the expression levels of hippocampal neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor in mice, activated the Nrf2, and the downstream heme oxygenase-1 (HO-1) a quintessential antioxidant enzyme. As rutin (quercetin-3-O-rutinose) was abundantly present in EAE and free quercetin was able to induce defensive antioxidant enzymes in an Nrf2-dependent manner, our findings suggested that quercetin derived from rutin via the intestinal microflora played a significant role in the protection of the mouse hippocampus from scopolamine-induced damage through BDNF-mediated Nrf2 activation, thereby dampening cognitive decline.

scholarly journals AZP2006, a new promising treatment for Alzheimer’s and related diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
N. Callizot ◽  
C. Estrella ◽  
S. Burlet ◽  
A. Henriques ◽  
C. Brantis ◽  
...  
Keyword(s):  
Therapeutic Application ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Potential Therapeutic Application ◽  
Promising Treatment ◽  
Central Synapses ◽  
First Time ◽  
Pgrn Level

AbstractProgranulin (PGRN) is a protein with multiple functions including the regulation of neuroinflammation, neuronal survival, neurite and synapsis growth. Although the mechanisms of action of PGRN are currently unknown, its potential therapeutic application in treating neurodegenerative diseases is huge. Thus, strategies to increase PGRN levels in patients could provide an effective treatment. In the present study, we investigated the effects of AZP2006, a lysotropic molecule now in phase 2a clinical trial in Progressive Supranuclear Palsy patients, for its ability to increase PGRN level and promote neuroprotection. We showed for the first time the in vitro and in vivo neuroprotective effects of AZP2006 in neurons injured with Aβ1–42 and in two different pathological animal models of Alzheimer’s disease (AD) and aging. Thus, the chronic treatment with AZP2006 was shown to reduce the loss of central synapses and neurons but also to dramatically decrease the massive neuroinflammation associated with the animal pathology. A deeper investigation showed that the beneficial effects of AZP2006 were associated with PGRN production. Also, AZP2006 binds to PSAP (the cofactor of PGRN) and inhibits TLR9 receptors normally responsible for proinflammation when activated. Altogether, these results showed the high potential of AZP2006 as a new putative treatment for AD and related diseases.

scholarly journals In Vitro Studies to Assess the α-Glucosidase Inhibitory Activity and Insulin Secretion Effect of Isorhamnetin 3-O-Glucoside and Quercetin 3-O-Glucoside Isolated from Salicornia herbacea

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 483
Author(s):  
Dahae Lee ◽  
Jun Yeon Park ◽  
Sanghyun Lee ◽  
Ki Sung Kang
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Ethanolic Extract ◽  
Ethyl Acetate Fraction ◽  
Gradient Elution ◽  
Glucosidase Activity ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion ◽  
Salicornia Herbacea

In this study, we examined the effect of ethanolic extract of Salicornia herbacea (ESH), isorhamnetin 3-O-glucoside (I3G), quercetin 3-O-glucoside (Q3G), quercetin, and isorhamnetin on α-glucosidase activity and glucose-stimulated insulin secretion (GSIS) in insulin-secreting rat insulinoma (INS-1) cells. A portion of the ethyl acetate fraction of ESH was chromatographed on a silica gel by a gradient elution with chloroform and methanol to provide Q3G and I3G. ESH, Q3G, and quercetin inhibited α-glucosidase activity, and quercetin (IC50 value was 29.47 ± 3.36 μM) inhibited the activity more effectively than Q3G. We further demonstrated that ESH, Q3G, quercetin, I3G, and isorhamnetin promote GSIS in INS-1 pancreatic β-cells without inducing cytotoxicity. Among them, I3G was the most effective in enhancing GSIS. I3G enhanced the phosphorylation of total extracellular signal-regulated kinase (ERK), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and activated pancreatic and duodenal homeobox-1 (PDX-1), which are associated with insulin secretion and β-cell function. As components of ESH, Q3G has the potential to regulate blood glucose by inhibiting α-glucosidase activity, and I3G enhances the insulin secretion, but its bioavailability should be considered in determining biological importance.

scholarly journals Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 985
Author(s):  
Luisa Müller ◽  
Nicole Power Guerra ◽  
Jan Stenzel ◽  
Claire Rühlmann ◽  
Tobias Lindner ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Neuroprotective Effect ◽  
Resonance Spectroscopy ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Positron Emission ◽  
Pet Ct ◽  
Amyloid Aβ ◽  
Β Amyloid

Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.

scholarly journals Ethanolic Extracts of Adlay Testa and Hull and Their Active Biomolecules Exert Relaxing Effect on Uterine Muscle Contraction through Blocking Extracellular Calcium Influx in Ex Vivo and In Vivo Studies

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 887
Author(s):  
Yun-Ju Huang ◽  
Yu-Chieh Chen ◽  
Hsin-Yuan Chen ◽  
Yi-Fen Chiang ◽  
Mohamed Ali ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Uterine Contraction ◽  
Calcium Influx ◽  
Ex Vivo ◽  
Ethanolic Extract ◽  
Ethyl Acetate Fraction ◽  
In Vivo Studies ◽  
Human Myometrium ◽  
Writhing Test

Dysmenorrhea is one of the most prevalent disorders in gynecology. Historically, adlay (Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been explored for its anti-tumor, pain relief, anti-inflammatory, and analgesic effects. The aim of this study was to evaluate the effects of adlay seeds on the inhibition of uterine contraction and thus dysmenorrhea relief, in vitro and in vivo. HPLC-MS and GC were used to elucidate the ethyl acetate fraction of adlay testa ethanolic extract (ATE-EA) and ethyl acetate fraction of adlay hull ethanolic extract (AHE-EA). Elucidation yielded flavonoids, phytosterols, and fatty acids. Uterine leiomyomas and normal adjacent myometrial tissue were evaluated by oxytocin- and PG-induced uterine contractility. ATE-EA and AHE-EA suppressed uterine contraction induced by prostaglandin F2 alpha (PGF2α), oxytocin, carbachol, and high-KCl solution ex vivo. In addition, the external calcium (Ca2+) influx induced contraction, and increased Ca2+ concentration was inhibited by ATE-EA and AHE-EA on the uterine smooth muscle of rats. Furthermore, ATE-EA and AHE-EA effectively attenuated the contraction of normal human myometrium tissues more than adjacent uterine leiomyoma in response to PGF2α. 3,5,6,7,8,3′,4′-Heptamethoxyflavone and chrysoeriol produced a remarkable inhibition with values of IC50 = 24.91 and 25.59 µM, respectively. The experimental results showed that treatment with ATE-EA at 30 mg/day effectively decreased the writhing frequency both on the oxytocin-induced writhing test and acetic acid writhing test of the ICR mouse.

scholarly journals Administration of Bifidobacterium breve Improves the Brain Function of Aβ1-42-Treated Mice via the Modulation of the Gut Microbiome

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1602
Author(s):  
Guangsu Zhu ◽  
Jianxin Zhao ◽  
Hao Zhang ◽  
Wei Chen ◽  
Gang Wang
Keyword(s):  
Gut Microbiome ◽  
Dietary Intervention ◽  
Neuroprotective Effects ◽  
Bifidobacterium Breve ◽  
Beneficial Effects ◽  
Behavioral Abnormalities ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
The Brain ◽  
Fibronectin Type

Psychobiotics are used to treat neurological disorders, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the mechanisms underlying their neuroprotective effects remain unclear. Herein, we report that the administration of bifidobacteria in an AD mouse model improved behavioral abnormalities and modulated gut dysbiosis. Bifidobacterium breve CCFM1025 and WX treatment significantly improved synaptic plasticity and increased the concentrations of brain-derived neurotrophic factor (BDNF), fibronectin type III domain-containing protein 5 (FNDC5), and postsynaptic density protein 95 (PSD-95). Furthermore, the microbiome and metabolomic profiles of mice indicate that specific bacterial taxa and their metabolites correlate with AD-associated behaviors, suggesting that the gut–brain axis contributes to the pathophysiology of AD. Overall, these findings reveal that B. breve CCFM1025 and WX have beneficial effects on cognition via the modulation of the gut microbiome, and thus represent a novel probiotic dietary intervention for delaying the progression of AD.

Modulation of longevity-associated genes by estrogens or phytoestrogens

2008 ◽  
Vol 389 (3) ◽  
pp. 273-277 ◽  
Author(s):  
Jose Viña ◽  
Juan Sastre ◽  
Federico V. Pallardó ◽  
Juan Gambini ◽  
Consuelo Borrás
Keyword(s):  
Superoxide Dismutase ◽  
Nuclear Factor Kappa B ◽  
Chemical Properties ◽  
Nuclear Factor ◽  
Antioxidant Protection ◽  
Beneficial Effects ◽  
Pathway Activation ◽  
Map Kinase Pathway ◽  
Kinase Pathway ◽  
Lower Peroxide

Abstract Females live longer than males. We have shown that the higher levels of estrogens in females protect them against aging, by up-regulating the expression of antioxidant, longevity-related genes, such as that of selenium-dependent glutathione peroxidase (GPx) and Mn-superoxide dismutase (Mn-SOD). Both estradiol and genistein (the most abundant phytoestrogen in soybeans) share chemical properties which confer antioxidant features to these compounds. However, the low concentration of estrogens and phytoestrogens make it unlikely that they exhibit significant antioxidant capacity in the organism. Physiological concentrations of estrogens and nutritionally relevant concentrations of genistein activate the MAP kinase pathway. These, in turn, activate the nuclear factor kappa B (NF-κB) signaling pathway. Activation of NF-κB by estrogens subsequently activates the expression of Mn-SOD and GPx, but genistein is only capable of activating Mn-SOD expression. This could be due to the fact that genistein binds preferably to estrogen receptor β. The antioxidant protection is reflected in the lower peroxide levels found in cells treated with estrogens or phytoestrogens when compared with controls. The challenge for the future is to find molecules that have the beneficial effects of estradiol, but without its feminizing effects. Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet this challenge.

Islet protective and insulin secretion property of Murraya koenigii and Ocimum tenuflorum in streptozotocin-induced diabetic mice

2012 ◽  
Vol 90 (3) ◽  
pp. 371-378 ◽  
Author(s):  
Menakshi Bhat Dusane ◽  
Bimba N. Joshi
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Immunohistochemical Analysis ◽  
Diabetic Mice ◽  
Murraya Koenigii ◽  
Cell Protection ◽  
Beneficial Effects ◽  
Endogenous Insulin ◽  
Muscle Tissues ◽  
Glucose 6 Phosphate Dehydrogenase

The present study investigates the antidiabetogenic effects of Murraya koenigii (L.) Spr. and Ocimum tenuflorum  L. on streptozotocin-induced diabetic Swiss mice. Treatment with extracts of M. koenigii (chloroform; MKC) and O. tenuflorum (aqueous; OTA) resulted in proper glucose utilization with an increase in liver glucose-6-phosphate dehydrogenase enzyme activity, and normal glycogenesis in hepatic and muscle tissues. Pancreatic and intestinal glucosidase inhibitory activity observed with MKC and OTA treatment indicated beneficial effects in reducing postprandial hyperglycemia with concomitant improvement in glucose metabolism. The glucosidase inhibition was prolonged, even after discontinuation of MKC and OTA treatment. Normalization of plasma insulin and C-peptide levels was observed in diabetic mice, indicating endogenous insulin secretion after treatment. The histochemical and immunohistochemical analysis of pancreatic islets suggests the role of MKC and OTA in pancreatic β-cell protection and the functional pancreatic islets that produce insulin. The study demonstrates the significance of MKC and OTA in glucosidase inhibition and islet protection in the murine diabetic model. These findings suggest the potential of the extracts in adjuvant therapy for the treatment of diabetes and the possible development of potential neutraceuticals.

scholarly journals Hepatic functions of GLP-1 and its based drugs: current disputes and perspectives

2016 ◽  
Vol 311 (3) ◽  
pp. E620-E627 ◽  
Author(s):  
Tianru Jin ◽  
Jianping Weng
Keyword(s):  
Insulin Resistance ◽  
Degradation Products ◽  
Hepatic Glucose Production ◽  
Wnt Signaling Pathway ◽  
Glucose Production ◽  
Metabolic Effects ◽  
Beneficial Effects ◽  
Metabolic Functions ◽  
Pathway Activation ◽  
Hepatic Glucose

GLP-1 and its based drugs possess extrapancreatic metabolic functions, including that in the liver. These direct hepatic metabolic functions explain their therapeutic efficiency for subjects with insulin resistance. The direct hepatic functions could be mediated by previously assumed “degradation” products of GLP-1 without involving canonic GLP-1R. Although GLP-1 analogs were created as therapeutic incretins, extrapancreatic functions of these drugs, as well as native GLP-1, have been broadly recognized. Among them, the hepatic functions are particularly important. Postprandial GLP-1 release contributes to insulin secretion, which represses hepatic glucose production. This indirect effect of GLP-1 is known as the gut-pancreas-liver axis. Great efforts have been made to determine whether GLP-1 and its analogs possess direct metabolic effects on the liver, as the determination of the existence of direct hepatic effects may advance the therapeutic theory and clinical practice on subjects with insulin resistance. Furthermore, recent investigations on the metabolic beneficial effects of previously assumed “degradation” products of GLP-1 in the liver and elsewhere, including GLP-128–36 and GLP-132–36, have drawn intensive attention. Such investigations may further improve the development and the usage of GLP-1-based drugs. Here, we have reviewed the current advancement and the existing controversies on the exploration of direct hepatic functions of GLP-1 and presented our perspectives that the direct hepatic metabolic effects of GLP-1 could be a GLP-1 receptor-independent event involving Wnt signaling pathway activation.

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