Evaluation of Dose-Dependent Obesity and Diabetes-Related Complications of Water Chestnut (Fruit of Trapa japonica) Extracts in Type II Obese Diabetic Mice Induced by 45% Kcal High-Fat Diet.

Background and Objectives: The currently used pharmacological agents for metabolic disorders such as type II diabetes have several limitations and adverse effects; thus, there is a need for alternative therapeutic drugs and health functional foods. Materials and Methods: This study investigated the pharmacological effects of water chestnut (fruit of Trapa japonica) extracts (WC: 50-200 mg/kg) for type II diabetes using a 45% Kcal high-fat diet (HFD)-fed type II obese diabetic mice model for a period of 84 days, and the effects were compared to those of metformin (250 mg/kg). Results: Increases in body weight, serum biochemical indices such as triglycerides, low-density lipoprotein, and blood urea nitrogen, increases in antioxidant defense system enzymes such as catalase, superoxide dismutase, and glutathione, and mRNA expressions (such as AMPKα1 and AMPKα2) in the liver tissue and mRNA expressions (such as AMPKα2 mRNA, leptin, and C/EBPα) in the adipose tissue were observed in the HFD control group. The WC (50 mg/kg)-administered group showed no significant improvements in diabetic complications. However, HFD-induced obesity and diabetes-related complications such as hyperlipidemia, diabetic nephropathy, nonalcoholic fatty liver disease (NAFLD), oxidative stress, activity of antioxidant defense systems, and gene expressions were significantly and dose-dependently inhibited and/or normalized by oral administration of WC (100 mg/kg and 200 mg/kg), particularly at a dose of 100 mg/kg. Conclusions: The results of this study suggest that WC at an appropriate dose could be used to develop an effective therapeutic drug or functional food for type II diabetes and various associated complications, including NAFLD.

Comparative Analysis of the Microbiome across the Gut-Skin Axis in Atopic Dermatitis.

Atopic dermatitis (AD) is a refractory and relapsing skin disease with a complex and multifactorial etiology. Various congenital malformations and environmental factors are thought to be involved in the onset of the disease. The etiology of the disease has been investigated, with respect to clinical skin symptoms and systemic immune response factors. A gut microbiome-mediated connection between emotional disorders such as depression and anxiety, and dermatologic conditions such as acne, based on the comorbidities of these two seemingly unrelated disorders, has long been hypothesized. Many aspects of this gut-brain-skin integration theory have recently been revalidated to identify treatment options for AD with the recent advances in metagenomic analysis involving powerful sequencing techniques and bioinformatics that overcome the need for isolation and cultivation of individual microbial strains from the skin or gut. Comparative analysis of microbial clusters across the gut-skin axis can provide new information regarding AD research. Herein, we provide a historical perspective on the modern investigation and clinical implications of gut-skin connections in AD in terms of the integration between the two microbial clusters.

Molecular mechanisms of cutis laxa- and distal renal tubular acidosis-causing mutations in V-ATPase a subunits, ATP6V0A2 and ATP6V0A4.

The a subunit is the largest of 15 different subunits that make up the vacuolar H+-ATPase (V-ATPase) complex, where it functions in proton translocation. In mammals, this subunit has four paralogous isoforms, a1-a4, which may encode signals for targeting assembled V-ATPases to specific intracellular locations. Despite the functional importance of the a subunit, its structure remains controversial. By studying molecular mechanisms of human disease-causing missense mutations within a subunit isoforms, we may identify domains critical for V-ATPase targeting, activity and/or regulation. cDNA-encoded FLAG-tagged human wildtype ATP6V0A2 (a2) and ATP6V0A4 (a4) subunits and their mutants, a2P405L (causing cutis laxa), and a4R449H and a4G820R (causing renal tubular acidosis, dRTA), were transiently expressed in HEK 293 cells. N-Glycosylation was assessed using endoglycosidases, revealing that a2P405L, a4R449H, and a4G820R were fully N-glycosylated. Cycloheximide (CHX) chase assays revealed that a2P405L and a4R449H were unstable relative to wildtype. a4R449H was degraded predominantly in the proteasomal pathway, whereas a2P405L was degraded in both proteasomal and lysosomal pathways. Immunofluorescence studies disclosed retention in the endoplasmic reticulum and defective cell-surface expression of a4R449H and defective Golgi trafficking of a2P405L Co-immunoprecipitation studies revealed an increase in association of a4R449H with the V0 assembly factor VMA21, and a reduced association with the V1 sector subunit, ATP6V1B1 (B1). For a4G820R, where stability, degradation, and trafficking were relatively unaffected, 3D molecular modeling suggested that the mutation causes dRTA by blocking the proton pathway. This study provides critical information that may assist rational drug design to manage dRTA and cutis laxa.

N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis.

The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. Previously, we have shown directly that the predicted sequon for the a4 isoform is indeed N-glycosylated. Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. Expression and N-glycosylation were characterized by immunoblotting and mobility shifts after enzymatic deglycosylation, and intracellular localization was determined using immunofluorescence microscopy. All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. Cycloheximide-chase experiments showed that unglycosylated subunits were turned over at a higher rate than N-glycosylated forms by degradation in the proteasomal pathway. Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes.

Protective effects of guggulsterone against colitis are associated with the suppression of TREM-1 and modulation of macrophages.

Triggering receptor expressed on myeloid cells 1 (TREM-1)-expressing intestinal macrophages are significantly increased in the colons of patients with inflammatory bowel disease (IBD). We focused here on the effects of guggulsterone on macrophage modulation in colitis as a potential therapeutic molecule in human IBD and explore the underlying mechanisms. Gene expression in macrophages was examined and wound-healing assay using HT-29 cells was performed. Colitis in wild-type and IL-10-, Toll-like receptor 4 (TLR4)-, and myeloid differentiation primary response 88 (MyD88)-deficient mice was induced via the administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the colon. In both in vitro and in vivo experiments, guggulsterone suppressed intestinal inflammation amplified by TREM-1 stimulation, in which the suppression of NF-κB, activating protein-1, and proteasome pathways was involved. In the TNBS-induced colitis model, guggulsterone reduced disease activity index scores and TREM-1 expression, stimulated IL-10 production, and improved survival in wild-type mice. These effects were not observed in IL-10-, TLR4-, and MyD88-deficient mice. Guggulsterone also suppressed M1 polarization, yet induced the M2 phenotype in macrophages from IBD patients as well as from mice. These findings indicate that guggulsterone blocks the hyperactivation of macrophages via TREM-1 suppression and induces M2 polarization via IL-10 mediated by the TLR4 signaling pathway. Furthermore, this study provides a new rationale for the therapeutic potential of guggulsterone in the treatment of IBD. NEW & NOTEWORTHY We found that guggulsterone attenuates triggering receptor expressed on myeloid cells 1 (TREM-1)-mediated hyperactivation of macrophages and polarizes macrophages toward the M2 phenotype. This was mediated by IL-10 and partly Toll-like receptor 4 signaling pathways. Overall, these data support that guggulsterone as a natural plant sterol modulates macrophage phenotypes in colitis, which may be of novel therapeutic importance in inflammatory bowel disease treatment.

Selective Ring Opening of 1-Methylnaphthalene Over NiW-Supported Catalyst Using Dealuminated Beta Zeolite.

Nanoporous Beta zeolite was dealuminated by weak acid treatment for reducing the acidity. Bi-functional catalysts were prepared using commercial Beta zeolites and the dealuminated zeolites for acidic function, NiW for metallic function. 1-Methylnaphthalene was selected as a model compound for multi-ring aromatics in heavy oil, and its selective ring opening reaction has been investigated using the prepared bi-functional catalysts with different acidity in fixed bed reaction system. The dealuminated Beta zeolites, which crystal structure and nanoporosity were maintained, showed the higher SiO2/Al2O3 ratio and smaller acidity than their original zeolite. NiW-supported catalyst using the dealuminated Beta zeolite with SiO2/Al203 mole ratio of 55 showed the highest performance for the selective ring opening. The acidity of catalyst seemed to play an important role as active sites for the selective ring opening of 1-methylnaphthalene but there should be some optimum catalyst acidity for the reaction. The acidity of Beta zeolite could be controlled by the acid treatment and the catalyst with the optimum acidity for the selective ring opening could be prepared.

The Effect of K and Acidity of NiW-Loaded HY Zeolite Catalyst for Selective Ring Opening of 1-Methylnaphthalene.

Bi-functional catalysts were prepared using HY zeolites with various SiO2/Al2O3 ratios for acidic function, NiW for metallic function, and K for acidity control. 1-Methylnaphthalene was selected as a model compound for multi-ring aromatics in heavy oil, and its selective ring opening reaction was investigated using the prepared bi-functional catalysts with different levels of acidity in a fixed bed reactor system. In NiW/HY catalysts without K addition, the acidity decreased with the SiO2/Al2O3 mole ratio of the HY zeolite. Ni1.1W1.1/HY(12) catalyst showed the highest acidity but slightly lower yields for the selective ring opening than Ni1.1W1.1/HY(30) catalyst. The acidity of the catalyst seemed to play an important role as the active site for the selective ring opening of 1-methylnaphthalene but there should be some optimum catalyst acidity for the reaction. Catalyst acidity could be controlled between Ni1.1W1.1/HY(12) and Ni1.1W1.1/HY(30) by adding a moderate amount of K to Ni1.1W1.1/HY(12) catalyst. K0.3Ni1.1W1.1/HY(12) catalyst should have the optimum acidity for the selective ring opening. The addition of a moderate amount of K to the NiW/HY catalyst must improve the catalytic performance due to the optimization of catalyst acidity.

The Effects of Topical Application of Polycal (a 2:98 (g/g) Mixture of Polycan and Calcium Gluconate) on Experimental Periodontitis and Alveolar Bone Loss in Rats.

The aim of this study was to observe whether Polycal has inhibitory activity on ligation-induced experimental periodontitis and related alveolar bone loss in rats following topical application to the gingival regions. One day after the ligation placements, Polycal (50, 25, and 12.5 mg/mL solutions at 200 µL/rat) was topically applied to the ligated gingival regions daily for 10 days. Changes in bodyweight, alveolar bone loss index, and total number of buccal gingival aerobic bacterial cells were monitored, and the anti-inflammatory effects were investigated via myeloperoxidase activity and levels of the pro-inflammatory cytokines IL-1ß and TNF-α. The activities of inducible nitric oxide synthase (iNOS) and lipid peroxidation (MDA) were also evaluated. Bacterial proliferation, periodontitis, and alveolar bone loss induced by ligature placements were significantly inhibited after 10 days of continuous topical application of Polycal. These results indicate that topical application of Polycal has a significant inhibitory effect on periodontitis and related alveolar bone loss in rats mediated by antibacterial, anti-inflammatory, and anti-oxidative activities.

Essential oils purified from Schisandrae semen inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 activation and migration of human aortic smooth muscle cells.

BACKGROUND: The migration of vascular smooth muscle cells from the tunica media to the subendothelial region may be a key event in the development of atherosclerosis after arterial injury. In this study, we investigated the potential mechanisms underlying the anti-atherosclerotic effects of Schisandrae Semen essential oil (SSeo) in human aortic smooth muscle cells (HASMCs). METHODS: Metalloproteinase-2/9 (MMP-2/9) activity was evaluated by gelatin zymography and gelatinase activity assay kit. The possible mechanisms underlying SSeo-mediated reduction of by tumor necrosis factor (TNF)-α-induced cell invasion and inhibition of secreted and cytosolic MMP-9 production in HASMCs were investigated. RESULTS: Our results indicate that SSeo treatment has an inhibitory effect on activation as well as expression of MMP-9 induced by TNF-α in HASMCs in a dose-dependent manner without significant cytotoxicity. SSeo attenuated nuclear translocation of TNF-α-mediated nuclear factor-kappa B (NF-κB) and blocked degradation of the NF-κB inhibitor proteins as well as the production of reactive oxygen species. SSeo also reduced TNF-α-induced production of pro-inflammatory mediators such as nitric oxide and prostaglandin E2 and inhibited inducible nitric oxide synthase and cyclooxygenase-2 expression in HASMCs. Furthermore, the Matrigel migration assay showed that SSeo effectively reduced TNF-α-induced HASMC migration compared with that in the control group. CONCLUSIONS: Taken together, these results suggest that SSeo treatment suppresses TNF-α-induced HASMC migration by selectively inhibiting MMP-9 expression, which was associated with suppression of the NF-κB signaling pathway. Taken together, these results suggest that SSeo has putative potential anti-atherosclerotic activity.

Genotoxicity of rice bran oil extracted by supercritical CO2 extraction.

Rice bran oil extracted by supercritical CO2 extraction (RB-SCE) reportedly exhibits pharmacological activities such as antioxidant and in vivo hair growth-inducing effects. Such activities raise the possibility of the development of novel hair growth-inducing agents using RB-SCE. The aim of this study was to investigate the potential genotoxic effects of RB-SCE in three short-term mutagenicity assays (bacterial reverse mutation assay, in vitro mammalian chromosomal aberration test, and in vivo micronucleus assay). RB-SCE showed no genotoxicity in the bacterial reverse mutation assay up to 5000 mg/plate and in the in vivo micronucleus test up to 600 mg/kg body weight. However, at 120 µg/mL with S9 mix and 200 µg/mL without S9 mix RB-SCE showed significantly different genotoxicity than the negative control in the in vitro chromosome aberration test. The induction of chromosomal aberrations under the present conditions may have no biological significance. We have herein demonstrated that RB-SCE can be regarded as a non-genotoxic material based on the available in vivo and in vitro results.

In vivo hair growth-promoting effect of rice bran extract prepared by supercritical carbon dioxide fluid.

The potential hair growth-promoting activity of rice bran supercritical CO2 extract (RB-SCE) and major components of RB-SCE, linoleic acid, policosanol, γ-oryzanol, and γ-tocotrienol, were evaluated with the histological morphology and mRNA expression levels of cell growth factors using real-time reverse transcriptase-polymerase chain reaction (PCR) in C57BL/6 mice. RB-SCE showed hair growth-promoting potential to a similar extent as 3% minoxidil, showing that the hair follicles were induced to be in the anagen stage. The numbers of the hair follicles were significantly increased. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and keratinocyte growth factor (KGF) were also significantly increased and that of transforming growth factor-ß (TGF-ß) decreased in RB-SCE-treated groups. Among the major components of RB-SCE, linoleic acid and γ-oryzanol induced the formation of hair follicles according to examination of histological morphology and mRNA expression levels of cell growth factors. In conclusion, our results demonstrate that RB-SCE, particularly linoleic acid and γ-oryzanol, promotes hair growth and suggests RB-SCE can be applied as hair loss treatment.

Single-dose oral toxicity of fermented rice extracts (FREs): a 14-day observation.

The aim of present research was to determine the acute oral toxicity of fermented rice extracts (FREs), in female and male ICR mice. To investigate the toxicity and identify target organs, FREs were orally administered once to male and female ICR mice at doses of 0 (vehicle control), 500, 1000, or 2000 mg/kg body weight (BW). Effects on mortality, BW, and clinical signs were monitored over 14 days, including changes in the weights and histopathological characteristics of 14 organs, as described in the Korea Food and Drug Administration (KFDA) Guidelines (2009-116, 2009). No treatment-related mortality was observed during the 14-day observation period in either gender. In addition, no FRE-related change was observed in BW or organ weight (OW), clinical indicators, or histopathological findings in this study. Our results suggest that the FRE is non-toxic in mice and is therefore likely to be safe for clinical use. The approximate LD and LD50 in mice after single oral dose of FRE are greater than 2000 mg/kg in female and male ICR mice. Additionally, no specific target organ or negative clinical indicator was detected in this study.

Synthesis of mesoporous SAPO-34 zeolite from mesoporous silica materials for methanol to light olefins.

Mesoporous SAPO-34 zeolites were synthesized by using as-prepared mesoporous silica material as both silica source and mesopore tailor. The mesoporous SAPO-34 zeolite materials thus obtained are characterized by a series of different techniques, including poweder X-ray diffraction pattern, nitrogen physisorption analysis, scanning electron micrograph, temperature programmed desorption of ammonia, and inductively coupled plasma atomic emission spectrometry. The resultant mesoporous SAPO-34 crystals exhibit sphere-like particle with zeolite layer units. The mesopore size distribution and particle size can be changed by amounts of silica source and water. The methanol-to-olefins (MTO) reactions using these mesoporous SAPO-34 zeolites are carried out with a fixed-bed reactor. Catalytic tests exhibit that the mesoporous SAPO-34 zeolite materials show high catalytic activity compared with the conventional SAPO-34 for MTO reaction. The better catalytic activity and longer life time of the mesoporous SAPO-34 catalysts in MTO are mainly due to the existence of the mesoporosity of SAPO-34 with small particle size.

Single oral dose toxicity test of polycalcium, a mixed composition of polycan and calcium lactate-gluconate 1:9 (G/G) in SD rat.

The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

Efficacy Confirmation Test of Black Cumin (Nigella sativa L.) Seeds Extract Using a High-Fat Diet Mouse Model.

To deal with the adverse effects associated with the use of currently available treatments for metabolic disorders, such as type 2 diabetes, there is a need to find an alternative drug compound. In the present study, we investigated the therapeutic potential of black cumin (Nigella sativa L.) seeds extract (BCS extract) for type 2 diabetes using a 45% Kcal-fed obese mouse model. The BCS extract at different doses (400-100 mg/kg) showed a dose-dependent improvement tendency in high-fat diet (HFD)-induced obesity, non-alcoholic fatty liver disease (NAFLD), hyperlipidemia, and diabetic nephropathy compared to the metformin (250 mg/kg). In particular, BCS extract at a dose of 200 mg/kg significantly inhibited the HFD-induced metabolic conditions. The oral administration of BCS extract (200 mg/kg) significantly inhibited the oxidative stress through lipid peroxidation, normalized the activity of sugar metabolism-related enzymes and the expression of genes involved in fat metabolism, and inhibited insulin resistance through glucose and fat metabolism by regulating the 5'-AMP-activated protein kinase (AMPK) expression. Furthermore, BCS extract (200 mg/kg) showed renal damage improvement effects compared to the metformin (250 mg/kg). The results clearly show that BCS aqueous extract at an appropriate concentration could help in the treatment of metabolic disorders, and BCS aqueous extract can be used as a functional food for various diabetic complications, such as obesity, diabetes, and NAFLD.

Validating the Health Benefits of Coffee Berry Pulp Extracts in Mice with High-Fat Diet-Induced Obesity and Diabetes.

The effects of coffee (Coffea arabica L.) berry pulp extracts (CBP extracts) on the improvement of diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD) were evaluated using various in vitro antioxidant activity assays and through a high-fat diet-induced mild diabetic obese mouse model. After an 84-day oral administration of CBP extracts (400-100 mg/kg), bioactivities were evaluated. The in vitro analysis showed the highest DPPH● scavenging activity of 73.10 ± 4.27%, ABTS● scavenging activity of 41.18 ± 1.14%, and SOD activity of 56.24 ± 2.81%, at a CBP extract concentration of 1000 µg/mL. The in vivo analysis of the CBP extracts showed favorable and dose-dependent anti-obesity, anti-diabetic, NAFLD, nephropathy, and hyperlipidemia refinement effects through hepatic glucose enzyme activity, 5'-AMP-activated protein kinase (AMPK) up-regulation, antioxidant activity, lipid metabolism-related gene expression, and pancreatic lipid digestion enzyme modulatory activities. This study shows that an appropriate oral dosage of CBP extracts could function as a potent herbal formulation for a refinement agent or medicinal food ingredient to control type 2 diabetes and related complications.

Immunomodulatory effects of Aureobasidium pullulans SM-2001 exopolymers on the cyclophosphamide-treated mice.

The immunomodulatory effects of exopolymers of Aureobasidium pullulans SM-2001 containing beta-1,3/1,6-glucan were evaluated on the cyclophosphamide (CPA)-treated mice. To induce immunosuppress, 150 and 110 mg/kg of CPA were intraperitoneally injected at 1 and 3 days before start of test material administrations, respectively. Exopolymers were subcutaneously or orally administered in a volume of 10 ml/kg, 4 times; 12-hr intervals from 24 hrs after second treatment of CPA. After treatment of exopolymers, the changes of thymus and spleen weights, splenic amounts of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10, thymic and splenic CD3+, CD4+, CD8+ and TNF-alpha+ cells were monitored in CPA-treated mice. As results of CPA treatment, dramatical decreases of the CD3+, CD4+, CD8+ and TNF-alpha+ cells were detected in thymus and spleen with decreases of thymus and spleen weights. In addition, decreases of splenic TNF-alpha, IL-1beta and IL-10 contents were also detected at flow cytometrical observations. However, oral and subcutaneous treatment of exopolymers effectively reduced the immunosuppressive changes induced by CPA. Therefore, it is concluded that exopolymers of A. pullulans can be effectively prevent the immunosuppress mediated, at least partially, recruitment of T cells and TNF-alpha+ cells or enhancement of their activity, and can provide effective prevention or treat regimes for the immunosuppress and related diseases such as cancer, sepsis and high-dose chemotherapy or radiotherapy.

Effects of Steaming and SiO2 Surface Passivation on SSZ-13 Zeolites in the Ethylene to Propylene Reaction.

SSZ-13 zeolite was modified by two kinds of post-treatment methods such as steaming and SiO2 surface passivation (silylation) for ETP catalyst with high activity. The former steaming treatment was conducted in the range of 400-700 °C, whereas the latter surfaces passivation was applied to a chemical liquid deposition (CLD) technique that uses various silylation agents such as tetramethylorthosilicate (TMOS), tetraethylorthosilicate (TEOS), and tetrabuthylorthosilicate (TBOS). Catalysts were characterized by powder-XRD, ICP, Ar-phsisorption, solid-state 27Al MAS NMR, and NH3-TPD, and their activities were tested in fixed bed reaction system. Regarding the effects of steaming temperature, the results show that a relatively higher selectivity is observed in SSZ-13 catalysts treated at proper steaming temperatures such as 450 and 500 °C compared to parent and other steam treated catalysts. For optimum surface passivation treatments for ETP reactions, one-step surface passivation using TEOS agents among various passivation agents led to enhanced propylene selectivity to 80% when compared with parent and other silylated SSZ-13 catalysts. However, a sequential passivation treatment with a TEOS agent was not highly affected by the reaction activity.

Anti-diabetic effects of blue honeyberry on high-fed-diet-induced type II diabetic mouse.

BACKGROUND/OBJECTIVE: The blue honeysuckle berry (Lonicera caerulea var. edulis L.) is a small deciduous shrub belonging to the Caprifoliaceae family that is native to Russia, China, Japan, and Korea. The berry of this shrub is edible, sweet and juicy and is commonly known as the blue honeyberry (BHB). This study examined the anti-diabetic potential of BHB on high-fat-diet-induced mild diabetic mice. The hypoglycemic, and nephroprotective effects of the 12-week oral administration of blue honeyberry extract were analyzed. MATERIALS/METHODS: The hypoglycemic effects were based on the observed changes in insulin, blood glucose, and glycated hemoglobin (HbA1c). Furthermore, the changes in the weight of the pancreas, including its histopathology and immunohistochemical investigation were also performed. Moreover, the nephroprotective effects were analyzed by observing the changes in kidney weight, its histopathology, blood urea nitrogen (BUN), and serum creatinine levels. RESULTS: The results showed that the high-fat diet (HFD)-induced control mice showed a noticeable increase in blood glucose, insulin, HbA1c, BUN, and creatinine levels. Furthermore, growth was observed in lipid droplet deposition related to the degenerative lesions in the vacuolated renal tubules with the evident enlargement and hyperplasia of the pancreatic islets. In addition, in the endocrine pancreas, there was an increase in the insulin-and glucagon-producing cells, as well as in the insulin/glucagon cell ratios. On the other hand, compared to the HFD-treated mice group, all these diabetic and related complications were ameliorated significantly in a dose-dependent manner after 84 days of the continuous oral administration of BHBe at 400, 200 and 100 mg/kg, and a dramatic resettlement in the hepatic glucose-regulating enzyme activities was observed. CONCLUSIONS: By assessing the key parameters for T2DM, the present study showed that the BHBe could act as a potential herbal agent to cure diabetes (type II) and associated ailments in HFD-induced mice.

Hepatoprotective effects of blue honeysuckle on CCl4-induced acute liver damaged mice.

The objective of this study was to evaluate the hepatoprotective effects of blue honeysuckle (BH) on carbon tetrachloride (CCl4)-induced acute hepatic damage in mice. The experiment used a total of 60 ICR mice, which were divided into six groups. Except for the intact control groups, all groups received a single intraperitoneal injection of CCl4 after a 7 day pre-treatment period with distilled water, BH extracts, or silymarin. Twenty-four hours after the CCl4 injection, the following observations, representative of classical oxidative stress-mediated centrolobular necrotic acute liver injuries, were observed: decreased body weight; small nodule formation and enlargement on the gross inspections with related liver weight increase; elevation of serum AST and ALT, increases in hepatic lipid peroxidation and related depletion of endogenous antioxidants and antioxidative enzymes; centrolobular necrosis; increases in apoptotic markers, lipid peroxidation markers, and oxidative stress markers. However, liver damage was significantly inhibited by the pre-treatment with BH extracts. The present study demonstrated that oral administration of BH extracts prior to exposure to CCl4 conferred favorable hepatoprotective effects. These results demonstrated that BHe possessed suitable properties for use as a potent hepatoprotective medicinal food.