Actinidia arguta Extract Containing Myo-Inositol Suppresses TNF-α-Induced VCAM-1 Expression and Monocyte Adhesion to Endothelial Cells via Inhibition of the PTEN/Akt/GSK-3ß and NF-κB Signaling Pathways.

The primary inflammatory process in atherosclerosis, a major contributor to cardiovascular disease, begins with monocyte adhering to vascular endothelial cells. Actinidia arguta (kiwiberry) is an edible fruit that contains various bioactive components. While A. arguta extract (AAE) has been recognized for its anti-inflammatory characteristics, its specific inhibitory effect on early atherogenic events has not been clarified. We used tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs) for an in vitro model. AAE effectively hindered the attachment of THP-1 monocytes and reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. Transcriptome analysis revealed that AAE treatment upregulated phosphatase and tensin homolog (PTEN), subsequently inhibiting phosphorylation of AKT and glycogen synthase kinase 3ß (GSK3ß) in HUVECs. AAE further hindered phosphorylation of AKT downstream of the nuclear factor kappa B (NF-κB) signaling pathway, leading to suppression of target gene expression. Oral administration of AAE suppressed TNF-α-stimulated VCAM-1 expression, monocyte-derived macrophage infiltration, and proinflammatory cytokine expression in C57BL/6 mouse aortas. Myo-inositol, identified as the major compound in AAE, played a key role in suppressing THP-1 monocyte adhesion in HUVECs. These findings suggest that AAE could serve as a nutraceutical for preventing atherosclerosis by inhibiting its initial pathogenesis.

D-pinitol alleviates diabetic cardiomyopathy by inhibiting the optineurin-mediated endoplasmic reticulum stress and glycophagy signaling pathway.

Diabetic cardiomyopathy (DCM) is an important complication resulting in heart failure and death of diabetic patients. However, there is no effective drug for treatments. This study investigated the effect of D-pinitol (DP) on cardiac injury using diabetic mice and glycosylation injury of cardiomyocytes and its molecular mechanisms. We established the streptozotocin-induced SAMR1 and SAMP8 mice and DP (150 mg/kg/day) intragastrically and advanced glycation end-products (AGEs)-induced H9C2 cells. H9C2 cells were transfected with optineurin (OPTN) siRNA and overexpression plasmids. The metabolic disorder indices, cardiac dysfunction, histopathology, immunofluorescence, western blot, and immunoprecipitation were investigated. Our results showed that DP reduced the blood glucose and AGEs, and increased the expression of heart OPTN in diabetic mice and H9C2 cells, thereby inhibiting the endoplasmic reticulum stress (GRP78, CHOP) and glycophagy (STBD1, GABARAPL1), and alleviating the myocardial apoptosis and fibrosis of DCM. The expression of filamin A as an interaction protein of OPTN downregulated by AGEs decreased OPTN abundance. Moreover, OPTN siRNA increased the expression of GRP78, CHOP, STBD1, and GABARAPL1 and inhibited the expression of GAA via GSK3ß phosphorylation and FoxO1. DP may be helpful to treat the onset of DCM. Targeting OPTN with DP could be translated into clinical application in the fighting against DCM.

Effects of a pinitol-rich Glycyrrhiza glabra L. leaf extract on insulin and inflammatory signaling pathways in palmitate-induced hypertrophic adipocytes.

Glycyrrhiza glabra roots have been well studied for their pharmacological activities, whereas less research has been conducted on liquorice aerial parts. Leaves represent a good source of D-pinitol, useful in the treatment of insulin resistance-related pathologies. Herein, we analyzed the in vitro effects of a D-pinitol-rich methanolic extract from Glycyrrhiza glabra leaves (GGLME) against lipotoxicity-related hypertrophy, inflammation, and insulin resistance in 3T3-L1 adipocytes exposed to palmitic acid (PA), comparing its activity with D-pinitol. GGLME pretreatment decreased lipid deposition, PPAR-γ, and NF-κB pathway induced by PA, similarly to D-pinitol, and improved insulin sensitivity, in presence or not of PA, increasing PI3K, pAkt, and GLUT1 levels. This study confirms that liquorice leaves, considered a waste of resource, could potentially be reused, and support further in vivo studies on animal and human models. In conclusion, liquorice leaves extract represents a potential candidate for prevention of metabolically induced inflammation, frequently leading to metabolic disorders.

A pinitol-rich Glycyrrhiza glabra L. leaf extract as functional supplement with potential in the prevention of endothelial dysfunction through improving insulin signalling.

Background: Glycyrrhyza glabra L. is one of the most popular medicinal plant in the world, its roots having been used since ancient times in many traditional medicines. On the contrary, scarce attention has been dedicated to liquorice aerial parts. Previous studies showed the presence of a large group of polyphenols and a consistent amount of d-pinitol in the leaf extract.Methods: The methanolic extract from G. glabra leaves was profiled for its content in polyphenols; the amount of d-pinitol was also measured with two independent methods (HPLC-ELSD and NMR). The extract was tested for its in vitro protective effects against insulin resistance-related endothelial dysfunction in human umbilical vein endothelial cells exposed to palmitic acid, which is the most prevalent saturated free fatty acid in circulation.Results: Methanolic extract from liquorice leaves has a protective effect against the lipotoxicity-associated alterations of insulin pathway in human endothelial cells, similarly to what observed with pure d-pinitol.Conclusions: Liquorice leaves are to be considered a waste product which gives a phytocomplex endowed with interesting potential therapeutic properties, moreover the use of a liquorice leaves phytocomplex rather than a pure compound allows avoiding a series of isolation/purification procedures and can be easily scaled up for industrial applications.

Hypoglycemic active principles from the leaves of Bauhinia holophylla: Comprehensive phytochemical characterization and in vivo activity profile.

Bauhinia holophylla leaves, also known as "pata-de-vaca", are traditionally used in Brazil to treat diabetes. Although the hypoglycemic activity of this medicinal plant has already been described, the active compounds responsible for the hypoglycemic activity have not yet been identified. To rapidly obtain two fractions in large amounts compatible with further in vivo assay, the hydroalcoholic extract of B. holophylla leaves was fractionated by Vacuum Liquid Chromatography and then purified by medium pressure liquid chromatography combined with an in vivo Glucose Tolerance Test in diabetic mice. This approach resulted in the identification of eleven compounds (1-11), including an original non-cyanogenic cyanoglucoside derivative. The structures of the isolated compounds were elucidated by nuclear magnetic resonance and high-resolution mass spectrometry. One of the major compounds of the leaves, lithospermoside (3), exhibited strong hypoglycemic activity in diabetic mice at the doses of 10 and 20 mg/kg b.w. and prevents body weight loss. The proton nuclear magnetic resonance (1H NMR) quantification revealed that the hydroalcoholic leaves extract contained 1.7% of lithospermoside (3) and 3.1% of flavonoids. The NMR analysis also revealed the presence of a high amount of pinitol (4) (9.5%), a known compound possessing in vivo hypoglycemic activity. The hypoglycemic properties of the hydroalcoholic leaves extract and the traditional water infusion extracts of the leaves of B. holophylla seem thus to be the result of the activity of three unrelated classes of compounds. Such results support to some extent the traditional use of Bauhinia holophylla to treat diabetes.

Activation of PI3K/Akt Signaling Pathway in Rat Hypothalamus Induced by an Acute Oral Administration of D-Pinitol.

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor.

Alpha-amylase as molecular target for treatment of diabetes mellitus: A comprehensive review.

The alpha (α)-amylase is a calcium metalloenzyme that aids digestion by breaking down polysaccharide molecules into smaller ones such as glucose and maltose. In addition, the enzyme causes postprandial hyperglycaemia and blood glucose levels to rise. α-Amylase is a well-known therapeutic target for the treatment and maintenance of postprandial blood glucose elevations. Various enzymatic inhibitors, such as acarbose, miglitol and voglibose, have been found to be effective in targeting this enzyme, prompting researchers to express an interest in developing potent alpha-amylase inhibitor molecules. The review mainly focused on designing different derivatives of drug molecules such as benzofuran hydrazone, indole hydrazone, spiroindolone, benzotriazoles, 1,3-diaryl-3-(arylamino) propan-1-one, oxadiazole and flavonoids along with their target-receptor interactions, IC50 values and other biological activities.

Effects of alpha-glucosidase-inhibiting drugs on acute postprandial glucose and insulin responses: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses. METHODS: We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models. RESULTS: The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (-1.5 mmol/l mean PPG [95% CI -1.9, -1.1] by acarbose, and -1.6 [-1.9, -1.4] by miglitol) as compared to individuals without diabetes (-0.4 [95% CI -0.5, -0.3] by acarbose, and -0.6 [-0.8, -0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43-54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes. CONCLUSIONS: The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions.

Therapeutic role of d-pinitol on experimental colitis via activating Nrf2/ARE and PPAR-γ/NF-κB signaling pathways.

Ulcerative colitis is a recrudescent intestinal inflammation coupled with diarrhea, weight loss, pus, and blood stool, which seriously impacts the quality of patient life. d-Pinitol, which can be a food supplement isolated from the food plant-like soybeans, Ceratonia siliqua Linn and Bruguiera gymnorrhiza, has been proved to show anti-oxidative and anti-inflammatory effects. However, the potential mechanism of d-pinitol still remains ill-defined contemporarily. In the current study, the therapeutic effect and potential mechanisms of d-pinitol against colitis were investigated. Oxidative stress and inflammation of experimental colitis were caused by 3% DSS treatment once daily for 7 days. During DSS treatment, the mice of the positive drug group and three other groups were orally administered SASP or d-pinitol once daily. Clinical symptoms were analyzed, and macroscopic scores were calculated. The levels of oxidative and inflammatory cytokines were measured using assay kits and RT-PCR. Additionally, the protein expression of the Nrf2/ARE pathway and PPAR-γ was measured by Western blot. Results showed that d-pinitol enormously alleviated DSS-induced bodyweight loss, colon shortening, and histological injuries, achieving a therapeutic efficacy superior to SASP. Moreover, the oxidative stress and colonic inflammatory response were mitigated. d-pinitol not only significantly activated the Nrf2/ARE signaling pathway via facilitating the translocation of Nrf2 from sitoplazma to cytoblast, upregulating the protein expression levels of GCLC, GCLM, HO-1, and NQO1, but also improved the PPAR-γ level by binding to the active site of PPAR-γ, when suppressing NF-κB p65 and IκBα phosphorylation. In conclusion, d-pinitol exhibited a dramatic anti-colitis efficacy by activating the Nrf2/ARE pathway and PPAR-γ. Hence, d-pinitol may be a promising therapeutic drug against UC in the future.

Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies and Supplementation.

Liver lipid accumulation is a hallmark of non-alcoholic fatty liver disease (NAFLD), broadly associated with insulin resistance. Inositols (INS) are ubiquitous polyols implied in many physiological functions. They are produced endogenously, are present in many foods and in dietary supplements. Alterations in INS metabolism seems to play a role in diseases involving insulin resistance such as diabetes and polycystic ovary syndrome. Given its role in other metabolic syndromes, the hypothesis of an INS role as a supplement in NAFLD is intriguing. We performed a systematic review of the literature to find preclinical and clinical evidence of INS supplementation efficacy in NAFLD patients. We retrieved 10 studies on animal models assessing Myoinosiol or Pinitol deficiency or supplementation and one human randomized controlled trial (RCT). Overall, INS deficiency was associated with increased fatty liver in animals. Conversely, INS supplementation in animal models of fatty liver reduced hepatic triglycerides and cholesterol accumulation and maintained a normal ultrastructural liver histopathology. In the one included RCT, Pinitol supplementation obtained similar results. Pinitol significantly reduced liver fat, post-prandial triglycerides, AST levels, lipid peroxidation increasing glutathione peroxidase activity. These results, despite being limited, indicate the need for further evaluation of INS in NAFLD in larger clinical trials.

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies.

BACKGROUND: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. OBJECTIVE: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. MATERIALS AND METHODS: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. RESULTS: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. CONCLUSION: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

The effect of voglibose on metabolic profiles in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials.

OBJECTIVE: The effect of voglibose on metabolic homeostasis is not well characterized. Therefore, we conducted a systematic review and meta-analysis of clinical trials assessing the effect of voglibose on metabolic profile in patients with type 2 diabetes mellitus (T2DM). METHODS: Systematic searches were conducted in PubMed, Scopus, Embase, Google Scholar, Web of Science and Cochrane Library to identify clinical trials assessing the effects of voglibose supplementation on cardio-metabolic profile from incept up to 29 July 2019. Data was pooled using fixed- or random-effect models and weighted mean difference (WMD) as the effect size. RESULTS: Eight clinical trials from 1094 reports, were eligible for inclusion. Pooled findings identified significant reductions in hemoglobin A1c (HbA1c) (WMD= -0.27; 95 %CI -0.49 to -0.05; P = 0.01; I2 = 64.8 %) and an increase in LDL-cholesterol levels (WMD=5.97 mg/dl, 95 % CI 0.88, 11.06, P = 0.02; I2 = 0.0 %). However, no evidence of effect for voglibose intake on T2DM patients was observed for: fasting blood sugar (FBS) (WMD -7.43 mg/dl; 95 %CI -16.56 to 1.71; P = 0.110; I2 = 69.3 %), serum insulin (WMD= -0.15 µU/mL; 95 %CI -0.89 to 0.60; P = 0.70; I2 = 0.0 %), total-cholesterol (WMD=2.82 mg/dl, 95 %CI -2.36 to 8.01, P = 0.70; I2 = 49.7 %), triglycerides (WMD= -7.07 mg/dl, 95 %CI -21.76 to 7.62, P = 0.34; I2 = 0.0 %), HDL-cholesterol levels (WMD= -2.10 mg/dl, 95 %CI -4.48 to 0.27, P = 0.08; I2 = 0.0 %,), body mass index (BMI) (WMD=0.09 kg/m2, 95 %CI -0.70 to 0.87; P = 0.87; I2 = 0.0 %), body weight (WMD= -0.42 kg, 95 %CI -0.84 to 0.00; P = 0.05; I2 = 0.0 %), and adiponectin levels (WMD = 0.32 µg/mL, 95 %CI -0.74 to 1.38; P = 0.55; I2 = 0.0 %). CONCLUSIONS: The current meta-analysis identified a decrease in HbA1c and an increase in LDL-cholesterol with administration of voglibose. However, no significant effect was observed on FBS, insulin, bodyweight, BMI, adiponectin, triglycerides, total- and HDL-cholesterol levels.

Inhibitory activity of traditional plants against Mycobacterium smegmatis and their action on Filamenting temperature sensitive mutant Z (FtsZ)-A cell division protein.

The study was designed to assess whether plant extracts / phytochemical (D-Pinitol) synergistically combine with antituberculosis drugs and act on Mycobacterium smegmatis (M. smegmatis) as well as assess their mode of action on Mycobacterium tuberculosis (M.tb) Filamenting temperature sensitive mutant Z (FtsZ) protein. Resazurin microtitre plate assay (Checker board) was performed to analyze the activity of plant extracts against M. smegmatis. Synergistic behaviour of plant extracts / D-Pinitol with Isoniazid (INH) and Rifampicin (RIF) were determined by time-kill and checker board assays. Elongation of M. smegmatis cells due to this treatment was determined by light microscopy. The effect of Hexane methanol extract (HXM) plant extracts on cell viability was determined using PI/SYTO9 dual dye reporter Live/Dead assay. Action of HXM plant extracts / D-Pinitol on inhibition of FtsZ protein was done using Guanosine triphosphatase (GTPase) light scattering assay and quantitative Polymerase Chain Reaction (qPCR). The Hexane-methanolic plant extract of Acacia nilotica, Aegle marmelos and Glycyrrhiza glabra showed antimycobacterial activity at 1.56 ± 0.03, 1.32 ± 0.02 and 1.25 ± 0.03 mg/mL respectively and that of INH and RIF were 4.00 ± 0.06 µg/mL and 2.00 ± 0.04 µg/mL respectively. These plant extracts and major phytochemical exudate D-Pinitol was found to act synergistically with antimycobacterial drugs INH and RIF with an FIC index ~ 0.20. Time-Kill kinetics studies indicate that, these plant extracts were bacteriostatic in nature. D-Pinitol in conjunction with INH and RIF exhibited a 2 Log reduction in the growth of viable cells compared to untreated. Attempt to elucidate their mode of action through phenotypic analysis indicated that these plant extracts and D-Pinitol was found to interfere in cell division there by leading to an abnormal elongated cellular morphology. HXM extracts and D-Pinitol synergistically combined with the first line tuberculosis drugs, INH and RIF, to act on M. smegmatis. The increase in the length of M. smegmatis cells on treatment with D-Pinitol and HXM extract of the plants indicated that they hinder the cell division mechanism thereby leading to a filamentous phenotype, and finally leading to cell death. In addition, the integrity of the bacterial cell membrane is also altered causing cell death. Further gene expression analysis showed that these plant extracts and D-Pinitol hampers with function of FtsZ protein which was confirmed through in vitro inhibition of FtsZ-GTPase enzymatic activity.

Quebrachitol from Rhizophora mucronata inhibits biofilm formation and virulence production in Staphylococcus epidermidis by impairment of initial attachment and intercellular adhesion.

Staphylococcus epidermidis is well recognized nosocomial pathogen in clinical settings for their implants associated infections. Biofilm and virulence production executes a S. epidermidis pathogenesis against host. Hence, interfering of biofilm formation has become an auspicious to control the pathogenesis of S. epidermidis. The present study evaluates antibiofilm potential of Rhizophora mucronata against S. epidermidis biofilms. Rhizophora mucronata leaves extract significantly inhibited the biofilm formation and quebrachitol was identified as an active compound responsible for the biofilm inhibition. Quebrachitol significantly inhibited biofilm formation at concentration dependent manner without exhibit non-bactericidal property. And, quebrachitol reduced the biofilm building components such as exopolysaccharides, lipase and proteins production. Confocal laser scanning microscopic studies obtained quebrachitol surface independent biofilm efficacy against S. epidermidis. Notably, quebrachitol significantly reduced S. epidermidis adherence on biotic (coated with type I collagen and fibrinogen) and abiotic (hydrophobic and hydrophilic) surfaces. Addition of quebrachitol inhibits autolysis mediated initial attachment and accumulation associated aggregation process. Moreover, quebrachitol significantly reduced the hydrolases virulence production which supports S. epidermidis invasion into the host. Furthermore, gene expression analysis revealed the ability of quebrachitol to downregulate the virulence genes expression which are mainly involved in biofilm formation and virulence production. The results obtained from the present study suggest that quebrachitol as an ideal candidate for the therapeutic action against S. epidermidis pathogenesis.

An Oviposition Stimulant for a Magnoliaceae-Feeding Swallowtail Butterfly, Graphium doson, from its Primary Host Plant, Michelia compressa.

Chemical examination of plant constituents responsible for oviposition by a Magnoliaceae-feeding butterfly, Graphium doson, was conducted using its major host plant, Michelia compressa. A methanol extract prepared from young leaves of the plant elicited a strong oviposition response from females. The methanolic extract was then separated by solvent partition into three fractions: CHCl3, i-BuOH, and aqueous fractions. Active substance(s) resided in both i-BuOH- and water-soluble fractions. Bioassay-guided further fractionation of the water-soluble substances by means of various chromatographic techniques led to the isolation of an oviposition stimulant. The stimulant was identified as D-(+)-pinitol on the basis of 13C NMR spectra and physicochemical properties. D-(+)-Pinitol singly exhibited a moderate oviposition-stimulatory activity at a dose of 150 µg/cm2. This compound was present also in another host plant, Magnolia grandiflora, in a sufficient amount to induce oviposition behavior of G. doson females. Certain cyclitols including D-(+)-pinitol have been reported to be involved in stimulation of oviposition by some Aristolochiaceae- and Rutaceae-feeding papilionid butterflies. A possible pathway of phytochemical-mediated host shifts in the Papilionidae, in which certain cyclitols could enact important mediators, is discussed in relation to the evolution of cyclitol biosynthesis in plants.

D-Pinitol Ameliorates Imiquimod-Induced PsoriasisLike Skin Inflammation in a Mouse Model via the NF-κB Pathway.

Psoriasis is an autoregulated immune and inflammation-based skin disease affecting approximately 3-4% of the worldwide population. Pinitol, conservatively used in ayurvedic medicine, has been shown to disclose an antiinflammatory effect, hold back the T-helper cells, and postpone cardiovascular diseases. In the present study we aimed to reveal the effect of D-pinitol on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model via the nuclear factor-κB (NF-κB) pathway genes. In the current study, we found that D-pinitol ameliorated the skin abrasion and abridged epithelial thickness, inflammation numbers, and collagen-occupied regions in IMQ-induced psoriasis-like mice. The same results (epithelial thickness, inflammation numbers, and collagen-occupied regions) we achieved in dorsal skin regions. In addition, D-pinitol modified the lipid profile and antioxidant enzyme levels, which means that the IMQ-induced group showed elevated malondialdehyde when compared to D-pinitol. Downregulated expression of glutathione, superoxide dismutase, and catalase in the IMQ-induced group was incomparable with D-pinitol, control, and standard group. Additionally, inflammatory and NF-kB pathway gene levels in the psoriatic mouse skin, which includes tumor necrosis factor-α, interleukin [IL]-6, IL-17A, IL-23,TRAF3, NIK, IKKα, and RelB, were dramatically increased or decreased by treatment with D-pinitol. Histological and morphometric studies disclose the efficiency of D-pinitol. Finally, we found that D-pinitol reserved the TRAF3, NIK, IKKα, and RelB in the psoriatic skin, signifying that it restrains the commencement of NF-κB signaling pathways. The present results suggest that D-pinitol could prove to have tremendous preventive potential against the treatment and prevention of inflammatory disease.

Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes.

Introduction: Alpha-glucosidase inhibitors (AGIs) - oral antihyperglycemic drugs, inhibit upper gastrointestinal enzymes that break down complex carbohydrates into glucose. As a result, the absorption of glucose is delayed, postprandial glucose reduced, and glycemic control improved.Areas covered: In this review, the authors describe the current recommendations on the use of the three major approved AGIs (acarbose, miglitol, voglibose). Efficacy and safety parameters together with ethnic considerations have been highlighted throughout the manuscript. The article also discusses potential diabetes prevention and cardiovascular effects of these medications.Expert opinion: The overall safety and efficacy of this class of drug appears to be high: AGIs do not increase the risk of hypoglycemia, do not cause weight gain; they also significantly improve postprandial hyperglycemia, have been associated with the reduction in risk factors for cardiovascular disease and may also delay the progression of prediabetes to T2DM. In general, we continue to believe that acarbose, miglitol, and voglibose should be used as third-line add on treatment options to other anti-hyperglycemic agents. However, this class can have earlier consideration in elderly and/or when metformin is contraindicated.

Health-Promoting Properties of Selected Cyclitols for Metabolic Syndrome and Diabetes.

Cyclitols play a particularly important role in cell functioning because they are involved in ion channel physiology, phosphate storage, signal transduction, cell wall formation, membrane biogenesis, osmoregulation and they have antioxidant activity. They are involved in the cell membranes as a phosphatidyl myo-inositol, an inositol triphosphate precursor, which acts as a transmitter that regulates the activity of several hormones, such as follicle-stimulating hormone, thyrotropin, and insulin. The aim of this paper is to characterize the selected cyclitols: myo-inositol, D-chiro-inositol, and D-pinitol in type-2 metabolic syndrome and diabetes treatment. Results and discussion: Cyclitols have certain clinical applications in the treatment of metabolic syndromes and are considered to be an option as a dietary supplement for the treatment or prevention of gestational diabetes mellitus and type-2 diabetes. Improved metabolic parameters observed after using cyclitols, like myo-inositol, in the treatment of polycystic ovary syndrome and type-2 diabetes suggest that they may have a protective effect on the cardiovascular system. Pinitol, together with myo-inositol,maybe responsible for improving lipid profiles by reducing serum triglyceride and total cholesterol. Pinitol is also well-researched and documented for insulin-like effects. Myo-inositol, D-chiro-inositol, and D-pinitol indicate a number of therapeutic and health-promoting properties.

Pinitol consumption improves liver health status by reducing oxidative stress and fatty acid accumulation in subjects with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic hepatic injury in the world. One of the most important therapeutic strategies for this disease is modulating oxidative stress. This study hypothesized that supplementation of pinitol might exert hepatic protective effects, by modulating oxidative stress in subjects with NAFLD. A randomized, double-blind controlled trial was conducted in 90 subjects with ultrasonography-proven NAFLD, who were randomly assigned to the placebo, low-dose (300 mg/d), or high-dose (500 mg/d) of pinitol for 12 weeks. The outcome measures were liver fat content, liver enzymes, fasting and postprandial lipids, and oxidative stress levels. To understand the underlying mechanism, plasma metabolomic analysis based on a gas chromatography/time-of-flight mass spectrometry and urinary pinitol analysis were also performed. The pinitol group showed significantly lower levels in liver fat content, plasma liver enzymes, fasting/postprandial urinary malondialdehyde levels, and postprandial triglycerides concentrations, but significantly higher in glutathione peroxidase level compared with the placebo group. The metabolomic analysis identified 27 differential metabolites involved in glycine/serine/threonine metabolism, alanine/aspartate/glutamate metabolism, D-glutamine/D-glutamate metabolism, and fatty acid synthesis, implicating the role of pinitol in glutathione-related lipid and energy metabolism. These results suggest that pinitol may exert modulatory effects upon energy and metabolic pathways by reducing oxidative stress and fatty acid accumulation, which can lead to hepatoprotective benefits in NAFLD subjects.

GC-MS analysis of D-pinitol in carob: Syrup and fruit (flesh and seed).

D-pinitol (3-O-methyl-D-chiro-inositol) is a well-known bioactive compound with anti-diabetic and anti-oxidant biological functions. A gas chromatography-mass spectrometry (GC-MS) method was developed for its quantitation in carob syrup, flesh and seed samples originated from Cyprus. The analysis was performed after derivatization of carbohydrates and polyols into trimethylsilyl ether derivatives. D-pinitol was determined in 13 carob syrup samples, in concentrations ranging 65.71 ±â€¯4.60 - 77.72 ±â€¯5.44 mg/g (mean: 68.58 ±â€¯4.80 mg/g, n = 13). In two commercial samples, it was determined in relative medium-low concentrations (21.96 ±â€¯1.54 and 44.71 ±â€¯3.13 mg/g), revealing possible adulteration; however, this needs further investigation. Similarly, it was determined in high concentrations in carob flesh samples, in concentrations ranging 53.20 ±â€¯3.72 - 54.58 ±â€¯3.82 mg/g (mean: 53.81 ±â€¯3.76 mg/g, n = 3). On the other hand, seed samples proved very poor in D-pinitol (