RESUMO
The present study aims to investigate the anti-inflammatory potential of the leaf hydroalcoholic extract of Piper betleoides C. DC., also known as "Jangli Paan" in Northeast India, using lipopolysaccharide (LPS)-treated both cell culture (RAW264.7, macrophage cells) and animal (albino rat) model of inflammation. Treatment with leaf hydroalcoholic extract of Piper betleoides (PBtE) dose-dependently (5, 10, and 20 µg/mL) decreased the secretion of pro-inflammatory (TNF-α, IL-6, and MCP-1) and increased anti-inflammatory (IL-4 and IL-10) cytokines in LPS-treated macrophages. Similarly, treatment with PBtE also prevented the alternation in mRNA expression of inflammatory markers (TNF-α, CCL-2, IL-6, and IL-10) in LPS-treated macrophages. Dose-dependent supplementation with PBtE further reduced the production of intracellular ROS and increased the phagocytosis efficacies in LPS-treated cells. Further in vivo studies demonstrated that treatment with PBtE dose-dependently (50, 100, and 200 mg/kg body weight) prevented the dysregulation of the secretion of inflammatory cytokines (TNF-α, IL-4, IL-6, and IL-10) and reduced the circulatory levels of prostaglandin (PGE2) and nitric oxide products (nitrite) in LPS-treated animals. In addition, alternation of blood cell profiling and the liver as well as kidney dysfunctions were also prevented by the treatment with PBtE in LPS-treated rats. The anti-inflammatory potential of PBtE was comparable to those seen in sodium diclofenac (positive control) treated group. LC-MS analyses showed piperine, piperlongumine, piperolactam-A, and dehydropipernonaline and GC-MS analyses demonstrated phytol, caryophyllene, and falcarinol as the phytochemicals present in Piper betleoides, which might play an important role in preventing inflammation and associated pathophysiology. Different treatments didn't cause any toxicity in cell culture and animal models. This study for the first time demonstrated the promising anti-inflammatory potential of the leaf hydroalcoholic extract of Piper betleoides.
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Edible insects possess several health enhancing properties and play an important role in human nutrition. Coridius chinensis is an edible insect that is considered food and claimed as traditional medicine. In the present study, nutritional contents, chemical composition, antioxidant, and anti-inflammatory properties of C. chinensis were analyzed. It was found that the insect sample contains 50.46% moisture, 44.65% protein, 4.45% carbohydrate, 39.42% crude fats, 3.53% ash and 576.11 (Kcal/100 g) energy. Our study highlighted the presence of a significant amount of phenol and flavonoids. The C. chinensis hydro-alcoholic extract showed high antioxidant property and anti-inflammatory activity. GCMS analysis identified 61 volatile compounds. LC-MS analysis of hydroalcoholic extract of C. chinensis revealed the presence of compounds such as etodolac glucuronide, morphine 3-glucuronide, ecgonine, ecgonine methyl ester, sufentanil, and palmitoyl ethanololamide. These findings suggest that C. chinensis species can be employed as a valuable food source with excellent therapeutic properties.
Assuntos
Insetos Comestíveis , Heterópteros , Animais , Humanos , Antioxidantes , Anti-Inflamatórios/farmacologia , ÍndiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hodgsonia heteroclita has been known as an important traditionally consumed medicinal plant of North-East India known to have antidiabetic properties. This study aims to investigate the effects of the ethanolic fruit extract of Hodgsonia heteroclita against hyperglycemia and hyperlipidemia by using streptozotocin (STZ) treated diabetic mice. MATERIALS AND METHODS: The fruits of H. heteroclita were collected from the various parts of Kokrajhar district, Assam India (Geographic coordinates: 26°24'3.85â³ N 90°16'22.30â³ E). Basic morphological evaluations were carried out by the Botanical Survey of India, Eastern circle, Shillong, who also certified and identified the plant. Hexane, chloroform, and ethanolic extracts of the fruit of H. heteroclita were investigated for α-amylase inhibition assay as a rapid screening tool for examining anti-diabetic activity. The efficacy of ethanolic extract at a dose of 100, 200, and 300 mg/kg body weight was tested for 21 days in STZ-induced diabetic mice. The body weight, fasting plasma glucose and serum lipids, and hepatic glycogen levels were measured in experimental animals to examine the antihyperglycemic and antihyperlipidemic efficacy of the extract. Both HPTLC and LC-MS analysis was performed to examine the phyotochemicals present in the ethanolic extract of H. heteroclita. RESULTS: It has been observed that treatment with the ethanolic extract dose-dependently reduced the plasma glucose levels, total cholesterol, low density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol, triglyceride, and increased the body weight, liver glycogens and high-density lipoprotein-cholesterol in STZ treated diabetic mice. HPTLC demonstrated the presence of triterpene compounds and LC-MS analysis revealed the presence Cucurbitacin I, Cucurbitacin E, and Kuguacin G as the triterpene phytoconstituents. CONCLUSION: The present study demonstrated that ethanolic fruit extract of H. heteroclita improved both glycemic and lipid parameters in mice model of diabetes.
Assuntos
Cucurbitaceae , Diabetes Mellitus Experimental , Triterpenos , Camundongos , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/análise , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Hipolipemiantes/análise , Glicemia , Frutas/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Diabetes Mellitus Experimental/tratamento farmacológico , Etanol/química , Glicogênio Hepático , Colesterol/farmacologia , Peso Corporal , Triterpenos/farmacologia , Estreptozocina/farmacologiaRESUMO
Diabetic retinopathy (DR) is the most common retinal disorder, developed in 35% of patients with diabetes mellitus. Lower serum levels of 25-hydroxyvitamin D are associated with the increased risk of developing DR. High doses of the active form of vitamin D (VD), on the contrary, for a long period of time may lead to hypercalcemia and an imbalance in the regulation of bone metabolism. Herein, we studied the efficacy of dextran-gated carboxyphenylboronic acid (CPBA)-functionalized mesoporous silica nanoparticles (MSNs) for glucose-sensitive delivery of 1,25-dihydroxyvitamin D3 to modulate cellular oxidative stress and inflammation for managing DR. The physical adsorption technique was employed to load VD onto nanoparticles (263.63 µg/mg (w/w)). In the presence of glucose, the dextran molecules detach from pores, allowing VD to release since glucose has 1,2-cis diol groups which have very high affinity to CPBA. Approximately 75% of VD was released upon exposure to 25 mM glucose at a time point of 10 h, demonstrating glucose-responsive delivery. Furthermore, MSN-CPBA was able to deliver VD in a glucose-dependent manner and improve the bioavailability of VD. In high-glucose-supplemented human retinal cells, MSN-CPBA increased the bioavailability of VD and reduced cellular oxidative stress and inflammation. The results suggested that the VD-loaded nanocarrier exerted remarkable therapeutic capacity in reducing the risk of developing DR. By using MSN-CPBA as a delivery platform with dextran gating, the research proposes an effective treatment approach for improving the bioavailability and effectiveness of a hydrophobic molecule in the treatment of DR.
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Diabetes Mellitus , Retinopatia Diabética , Nanopartículas , Humanos , Dextranos , Retinopatia Diabética/tratamento farmacológico , Dióxido de Silício/química , Glucose , Nanopartículas/uso terapêutico , Nanopartículas/química , Vitamina D/uso terapêutico , InflamaçãoRESUMO
Mesoporous silica nanoparticles (MSNs) are promising nanomaterials that are widely used in biomedical applications like drug delivery, diagnosis, bio-sensing and cell tracking. MSNs have been investigated meticulously in the drug-delivery field due to their unique chemical and pharmacokinetic properties, such as highly ordered mesopores, high surface area and pore volume, tuneable pore size, stability, surface functionalisation, and biocompatibility. MSN-based nanocomposites have been used to deliver therapeutic molecules like insulin, GLP-1, exenatide, DPP-4 inhibitor and plasmid-containing GLP-1 genes for managing diabetes mellitus for the last decade. The functionalisation properties of MSNs make them substantially capable of the co-delivery, controlled delivery and stimuli-responsive delivery of antidiabetic drugs. This review focuses on the delivery of antidiabetic therapeutics with special emphasis on the functionalisation of MSNs and stimuli-responsive delivery.
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Nanopartículas , Dióxido de Silício , Dióxido de Silício/química , Hipoglicemiantes/uso terapêutico , Porosidade , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Portadores de Fármacos/químicaRESUMO
The present study investigated the antidiabetic potential of protein isolates from Hawaijar (HPI), a popular fermented soybean food of North-East India. Treatment with HPI significantly upregulated glucose uptake, glucose utilization, glucose-6-phosphate, and stimulated PI3K/AKT/GLUT4 pathway in high-glucose (HG)-treated myotubes. Signal silencing studies demonstrated that knockdown of insulin-dependent signaling molecule (IR) but not insulin-independent signaling molecule (AMPK) significantly inhibited HPI-induced activation of PI3K/AKT/GLUT4 pathway and glucose uptake in HG-treated myotubes. SDS-PAGE and immunoblotting analyses of HPI showed the reduction and/or absence of various subunits of 7S and 11S globulin protein and appearance of new proteins compared to respective non-fermented soy protein isolates. Using various chromatographic techniques, the present study further isolated a single protein (ISP, ~24 kDa) from HPI as one of the bioactive principles with promising glucose utilization potential via stimulating PI3K/AKT/GLUT4 pathway in HG-treated cells. ISP treatment along with insulin significantly stimulated PI3K/AKT/GLUT4 pathway and glucose uptake compared to either insulin or ISP alone treated cells against HG exposure suggesting the insulin sensitizing effect of ISP. Furthermore, ISP supplementation significantly reduced metabolic markers linked with diabetes in high-fructose high-fat diet-fed animal model of type 2 diabetes. This study demonstrated a novel molecular mechanism underlying the promising antidiabetic potential of HPI.
Assuntos
Diabetes Mellitus Tipo 2 , Alimentos de Soja , Animais , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Insulina/metabolismo , Fibras Musculares Esqueléticas , Suplementos Nutricionais , Índia , Transportador de Glucose Tipo 4/metabolismoRESUMO
PURPOSE: Seroepidemiology and genomic surveillance are valuable tools to investigate infection transmission during a pandemic. North East (NE) India is a strategically important region being the gateway connecting the country with Southeast Asia. Here, we examined the spread of SARS-CoV-2 in NE India during the first and second waves of COVID-19 using serological and whole genome sequencing approaches. METHODS: qRT-PCR analysis was performed on a selected population (n â= â16,295) from June 2020 to July 2021, and metadata was collected. Immunoassays were studied (n â= â2026) at three-time points (August 2020, February 2021, and June 2021) and in a cohort (n â= â35) for a year. SARS-CoV-2 whole genomes (n â= â914) were sequenced and analyzed with those obtained from the databases. RESULTS: Test positivity rates (TPR) in the first and second waves were 6.34% and 6.64% in Assam, respectively, and a similar pattern was observed in other NE states. Seropositivity in the three time points was 10.63%, 40.3%, and 46.33%, respectively, and neutralizing antibody prevalence was 90.91%, 52.14%, and 69.30%, respectively. Persistence of pan-IgG-N SARS-CoV-2 antibody for over a year was observed among three subjects in the cohort group. Normal variants dominated the first wave, while B.1.617.2 and AY-sublineages dominated the second wave in the region. The prevalence of the variants co-related well with high TPR and seropositivity rate in the region and identified mostly among vaccinated individuals. CONCLUSION: The COVID-19 first wave in the region witnessed low transmission with the evolution of diverse variants. Seropositivity increased during the study period with over half of the individuals carrying neutralizing antibodies against SARS-CoV-2. High infection and seroprevalence in NE India during the second wave were associated with the dominant emergence of variants of concern.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Estudos Soroepidemiológicos , SARS-CoV-2/genética , COVID-19/epidemiologia , Genômica , Índia/epidemiologia , Anticorpos NeutralizantesRESUMO
This study examined the antidiabetic efficacy of popular fermented soybean foods (FSF) of Northeast (NE) India. Results showed that among different FSF, aqueous extract of Hawaijar (AEH), a traditional FSF of Manipur, NE India, significantly augmented glucose utilization in cultured myotubes treated with high glucose (HG, 25 mM). Furthermore, AEH also upregulated glucose uptake, glucose-6-phosphate level, and phopho-PI3K/phospho-AKT/phospho-AMPK/GLUT4 protein expression in HG-treated myotubes. In vivo studies demonstrated that AEH supplementation (50, 100, or 200 mg/kg body weight/day, oral gavaging, 16 weeks) reduced body weight, fasting blood glucose, glycated hemoglobin, insulin resistance, and glucose intolerance in rats fed with high-fat diet (HFD). AEH supplementation stimulated phopho-PI3K/phospho-AKT/phospho-AMPK/GLUT4 signaling cascades involved in glucose metabolism of muscle tissues in diabetic rats. Chemical profiling of AEH (SDS-PAGE, immunoblotting, and HRMS) suggests the possible role of bioactive proteins/peptides and isoflavones underlying the antihyperglycemic potential AEH. Results from this study will be helpful for developing food-based prophylactics/therapeutics in managing hyperglycemia. PRACTICAL APPLICATIONS: Fermented soybean foods are gaining acceptance due to multiple health benefits. This study for the first time reports the antidiabetic potential of Hawaijar, an indigenous fermented soybean food of North-East India. Higher abundance of bioactive compounds (isoflavones and proteins/peptides) in Hawaijar may be responsible for the alleviation of impaired glucose metabolism associated with diabetes. The findings may be helpful for the development of a novel therapeutic to achieve better control of hyperglycemia and improve the lives of the patient population with diabetes.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hiperglicemia , Isoflavonas , Ratos , Humanos , Animais , Hipoglicemiantes/farmacologia , Glucose/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Glycine max/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Índia , Transdução de Sinais , Músculos/metabolismo , Hiperglicemia/tratamento farmacológicoRESUMO
Fermented soy foods (FSF) are gaining significant attention due to promising health benefits. In recent years, FSF are being studied extensively due to the presence of diverse functional ingredients including active isoflavones and peptides along with essential micronutrients. The process of fermentation is responsible for the enrichment of various bioactive principles in soy-based fermented foods and exclusion of some anti-nutrient factors which are found predominantly in raw soybeans. Emerging evidence suggests that FSF possess immense therapeutic potential against inflammation and associated pathological complications. Extracts prepared from various FSF (e.g. fermented soy paste, milk, and sauce) were found to exert promising anti-inflammatory effects in numerous in vitro and in vivo settings. Moreover, clinical findings highlighted an inverse relationship between consumption of FSF and the prevalence of chronic inflammatory disorders among the communities which habitually consume fermented soy products. Molecular mechanisms underlying the anti-inflammatory role of FSF have been delineated in many literatures which collectively suggest that FSF extracts have regulatory actions over the expression and/or activity of several proinflammatory cytokines, inflammatory mediators, oxidative stress markers, and some other factors involved in the inflammatory pathways. The present review discusses the anti-inflammatory effects of FSF with mechanistic insights based upon the available findings from cell culture, preclinical, and clinical investigations.
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Alimentos Fermentados , Isoflavonas , Alimentos de Soja , Anti-Inflamatórios/farmacologia , Isoflavonas/farmacologia , Glycine max/químicaRESUMO
Soybean (Glycine max) harbours high quality proteins which have been evident to exhibit therapeutic properties in alleviating many diseases including but not limited to diabetes and its related metabolic complications. Since diabetes is often manifested with hyperglycemia, impaired energy homeostasis and even low-grade chronic inflammation, plenty of information has raised the suggestion for soy protein supplementation in preventing and controlling these abnormalities. Moreover, clinical intervention studies have established a noteworthy correlation between soy protein intake and lower prevalence of diabetes. Besides soy protein, various soy-derived peptides also have been found to trigger antidiabetic response in different in vitro and in vivo models. Molecular mechanisms underlying the antidiabetic actions of soy protein and peptide have been predicted in many literatures. Results demonstrate that components of soy protein can act in diversified ways and modulate various cell signaling pathways to bring energy homeostasis and to regulate inflammatory parameters associated with diabetic pathophysiology. The main objective of the present review lies in a systemic understanding of antidiabetic role of soy protein and peptide in the context of impaired glucose and lipid metabolism, and inflammation.
Assuntos
Glycine max/química , Hipoglicemiantes/farmacologia , Peptídeos/farmacologia , Proteínas de Soja/farmacologia , Animais , Glicemia/efeitos dos fármacos , Estudos Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Especificidade de Órgãos/efeitos dos fármacos , Peptídeos/química , Peptídeos/uso terapêutico , Proteínas de Soja/química , Proteínas de Soja/uso terapêuticoRESUMO
The coronavirus disease 19 (COVID-19) has turned out to be a pandemic in short period of time due to the high transmissibility of its causative agent, severe acute respiratory syndrome coronavirus 2. Various reports have suggested the promising link between overexpression of angiotensin converting enzyme 2 (ACE2) and COVID-19 pathogenesis. The severity of COVID-19 pathophysiology is greatly depended on several comorbidities, like hypertension, diabetes mellitus (DM), respiratory and cardiovascular disease, out of which DM has emerged as a major risk factor. The current review focuses on the link among the expression of ACE2, use of ACE inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), and risk of COVID-19 pathogenesis in DM. The review also emphasizes on synergistic detrimental effect of DM and COVID-19 on the immune system in provoking uncontrolled cytokine storm which eventually leads to lethal consequences. Finally, several possible therapeutic strategies have been highlighted to reduce the excess of risk associated with COVID-19 in people with DM.
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COVID-19 , Diabetes Mellitus , Antagonistas de Receptores de Angiotensina/uso terapêutico , Enzima de Conversão de Angiotensina 2 , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19/complicações , Síndrome da Liberação de Citocina , Complicações do Diabetes , Diabetes Mellitus/patologia , Humanos , Sistema Renina-Angiotensina , Fatores de RiscoRESUMO
Role of growth arrest-specific 6 (Gas6), member of vitamin K (VK)-dependent protein family in hyperlipidemia-associated inflammation remains unresolved. To address this, blood samples were collected from hyperlipidemic subjects and age-matched healthy controls and observed that gamma-glutamyl carboxylated Gas6 (Gla-Gas6) but not total Gas6 were significantly lower while pro-inflammatory markers, MCP-1 and ICAM-1 were remarkably higher in hyperlipidemic subjects compared to control. Correlation analyses demonstrated that Gla-Gas6 levels were inversely correlated with MCP-1 and ICAM-1 but positively with plasma VK in hyperlipidemic subjects but not in control. This suggests that boosting VK level might ameliorate the hyperlipidemia-associated inflammatory pathophysiology via augmenting Gla-Gas6. Further studies with high fat diet (HFD)-fed mice demonstrated that VK supplementation (1, 3, and 5 µg/kg BW, 8 weeks) dose-dependently reduced both hepatic and plasma levels of MCP-1 and ICAM-1 while elevating that of Gla-Gas6 but not total Gas6 in HFD-fed mice. Cell culture studies with gamma-glutamyl carboxylase (enzyme causes VK-dependent carboxylation of Gas6) knockdown hepatocytes and monocytes dissected the direct role of Gla-Gas6 in inhibiting high palmitic acid (0.75 mM)-induced inflammation via arresting MCP-1/ICAM-1 mediated hepatocyte-monocyte adhesion. The present study demonstrated an important role of Gla-Gas6 in facilitating the prophylactic effect of VK against hyperlipidemia associated inflammation.
Assuntos
Quimiocina CCL2/metabolismo , Hiperlipidemias/complicações , Inflamação/tratamento farmacológico , Molécula 1 de Adesão Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Vitamina K/farmacologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Quimiocina CCL2/genética , Doença Crônica , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/fisiologia , Humanos , Inflamação/etiologia , Molécula 1 de Adesão Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Monócitos/fisiologiaRESUMO
The genus Vailimia Kammerer, 2006 is recorded for the first time from India. Two new species, Vailimia ajmerensis Caleb Jangid sp. nov. (â), and V. jharbari Basumatary, Caleb Das sp. nov. (ââ), are described and illustrated in detail. Presently, the genus is known only by the males, which means that the female of V. jharbari described herein is the first female known in the genus.
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Aranhas , Animais , Feminino , Índia , MasculinoRESUMO
Chitosan, a promising carbohydrate biopolymer is gaining scientific attention in a wide range of biomedical applications due to its outstanding chemical and pharmacokinetic properties. Recently, various studies have demonstrated the beneficial activities of chitosan in protecting and proliferating pancreatic beta cells, lowering hyperglycemia, and preventing impaired lipid metabolism associated diabetes mellitus. Moreover, chitosan has also been used in formulating several types of micro/nano-carriers for the delivery of different antidiabetic drugs, like insulin, GLP1, exendin-4, DPP-4 inhibitor, and plasmid encoding insulin or GLP to reduce hyperglycemia. This review for the first time provides an overview of the currently available evidences on the potential benefits of chitosan in managing diabetes mellitus and also emphasizes on the chitosan-based micro/nano-carriers in delivery of various antidiabetic drugs via oral, nasal, and subcutaneous routes. The outcome of this review will be helpful for the development of a novel therapeutic to achieve better control of diabetes mellitus.
Assuntos
Quitosana/química , Diabetes Mellitus/tratamento farmacológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Hipoglicemiantes/administração & dosagem , Nanopartículas/administração & dosagem , Humanos , Hipoglicemiantes/química , Nanopartículas/químicaRESUMO
The role of gamma-glutamyl-carboxylated growth arrest-specific 6 (cGas6) in mediating the beneficial effect of vitamin K (VK) on regulating glucose metabolism remains elusive. We took a three-pronged approach-evaluating human type 2 diabetes (T2D), high-fat diet (HFD)-fed mice, and in vitro cultured myotubes-to address this. Blood samples were collected from both T2D patients and control subjects; skeletal muscle and blood samples were collected from HFD-fed mice with or without VK supplementation (1, 3, and 5 µg/kg BW, 8 weeks); and the molecular mechanism of cGas6 was dissected using GGCX, Gas6, AXL, or IR siRNA-transfected cultured myotubes. Plasma cGas6 and VK were significantly lower in T2D patients compared with control; and cGas6 and the cGas6/Gas6 ratio were positively correlated with VK and inversely correlated with fasting glucose in T2D patients, suggesting an important role for plasma VK and cGas6 in maintaining glucose homeostasis in T2D. Animal studies revealed that VK supplementation dose-dependently upregulated plasma cGas6; stimulated the protein expression of cGas6, PI3K, pAKT, and GLUT4 in skeletal muscle; and reduced hyperglycemia in HFD-fed T2D mice. And in vitro mRNA knockdown studies demonstrated the requirement of cGas6 in mediating the positive effect of VK on glucose metabolism via stimulating the PI3K/pAKT/GLUT4 signaling pathway in high glucose-treated myotubes. These results demonstrate a significant involvement of cGas6 in mediating the beneficial effect of VK on regulating glucose homeostasis in T2D.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Hiperglicemia/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Vitamina K/administração & dosagem , Adulto , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hiperglicemia/tratamento farmacológico , Masculino , Camundongos , Pessoa de Meia-IdadeRESUMO
Insect-based bioactive components are emerging as novel sources of drugs, effective against various diseases. Inflammation is considered to be an innate immune response developed by different organisms against foreign pathogens and cellular stress. However, repetitive elevated inflammation is considered to be responsible for development of many other diseases including colitis and arthritis. Due to the limited activities and side effects of non-steroidal anti-inflammatory drugs, researchers are continuously looking for alternative sources of drug molecules to alleviate the inflammatory related complications. Recently, insect-based bioactive components, such as venoms, haemocytes, cecropin A, papiliocin, N-acetyldopamine dimers, cecropin-TY1 peptide, cop A3 peptide, glycosaminoglycan, coprisin peptide, silk fibroin microparticles, and silk fibroin nanoparticles have been found to be active against different inflammatory mechanisms and associated diseases. Cancers, are some of the deadliest diseases, which are mainly treated by chemotherapy, radiation therapy and surgery. However, such treatments, mainly chemotherapy, is associated with enormous side effects. Therefore, as an alternative, less hazardous option, compounds from insects with anti-cancerous activity are being explored. Insect-derived compounds, such as cantharidin, norcantharidin, isocoumarin, plancyols A, plancypyrazine A, pancratistatin, narciclasine, and ungeremine, show potential anti-cancerous activity. In this review, we will be discussing the role of different potential drug molecules of insect origin with special emphasis on anti-inflammation and their association with health disorders and cancer.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Inflamação/complicações , Insetos/química , Animais , Artrite/tratamento farmacológico , Artrite/etiologia , Produtos Biológicos/farmacologia , Colite/tratamento farmacológico , Colite/etiologia , Humanos , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/etiologiaRESUMO
The present study for the first time aims to examine the hypothesis that circulating gamma-glutamyl carboxylated growth arrest specific protein 6 (Gla-Gas6) deficiency may be associated with hyperlipidemia and vitamin K (VK) supplementation may ameliorate the impaired lipid homeostasis via activating Gas6 protein. Subjects with hyperlipidemia (n=22) and age-matched healthy controls (n=19) were included in this study. Results showed that plasma levels of Gla-Gas6 protein and VK were significantly lower in hyperlipidemic subjects compared to control. Moreover, Gla-Gas6 levels were significantly and positively correlated with VK (P=.034, r=0.452) and negatively with triglyceride (P=.022, r=-0.485) and total cholesterol (P=.043, r=-0.435) in hyperlipidemic subjects, which suggest that VK supplementation may have a positive effect in activating Gas6 protein and thereby reducing the aberrant plasma lipid levels. Further studies with high-fat diet (HFD)-fed animal model of hyperlipidemia demonstrated that VK supplementation (5 µg/kg body weight, 8 weeks) reduced the plasma lipid levels, stimulated both the plasma levels and the hepatic protein expression of Gla-Gas6 protein, and regulated the AMPK/SREBP1/PPARα signaling pathways of hepatic lipid metabolism in HFD-fed mice. Moreover, by using palmitic acid (PA, 0.75 mM)-treated both control and GGCX knockdown hepatocytes, this study dissected the direct role of Gla-Gas6 in mediating the positive effect of VK on preventing the PA-induced impaired hepatic lipid metabolism via regulating AMPK/SREBP1/PPARα pathways. Combining all, the present study demonstrated the beneficial effect of VK supplementation in preventing the impaired lipid homeostasis via activating VK-dependent Gas6 protein.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , PPAR alfa/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Vitamina K/metabolismo , Animais , Sobrevivência Celular , Feminino , Hepatócitos/metabolismo , Homeostase , Humanos , Hiperlipidemias/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Metabolismo dos Lipídeos , Masculino , Camundongos , Pessoa de Meia-Idade , Ácido Palmítico/metabolismo , Transdução de Sinais , Triglicerídeos/metabolismoRESUMO
Carbonaceous aerosols (CAs) are ubiquitous and among the most significant environmental materials found in ambient air, mainly derived from anthropogenic sources (biomass burning, industrial activity, vehicle emissions, etc.). Elemental carbon (black carbon) and organic carbons are the major constituents of CAs. Due to their toxic effects, they are considered as high-risk compounds for human health. The key objective of the present work is to conduct a feasibility study for the conversion of CAs (TSP and PM10) into a value-added carbon nanostructured product by using a chemical method. High resolution-transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), Raman spectroscopy, Fourier transforms infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), ultraviolet-visible spectroscopy (UV-visible), fluorescence spectroscopy (FL), and Zeta potential analyses indicated the formation of carbon nanomaterials with crystalline phases, which exhibit the characteristics of nanodiamonds (NDs). The HR-TEM image analysis showed that the nominal size of the CAs-derived NDs ranged from 4 to 17â¯nm composed of mainly carbon and oxygen. The FT-IR and XPS analysis indicated that the NDs are highly functionalized with an oxygen-containing functional group. The CAs-derived NDs showed the property of blue-fluorescence with excitation dependent. In the cytotoxicity and genotoxicity study, the NDs obtained was observed to be biocompatible and suitable for bioimaging applications. This result provides a new avenue for the conversion of CAs to high-value products leading to the mitigation of atmospheric pollution.
RESUMO
This study aims to examine the hypothesis that circulatory heavy metals may be associated with lung function decline and lower plasma GST activity and GSH level in COPD patients via activating monocytes mediated by impairing the NOX4/Nrf2/GCLC/GST signaling pathway. Results showed that the blood levels of heavy metals (cadmium, lead, mercury, and chromium) were significantly higher in COPD patients of coal mine site compared to the healthy controls. The levels of heavy metals in COPD patients were significantly and negatively correlated with lung function, GST activity, and GSH level. Using flowcytometry, fluorescence spectroscopy, and immunoblotting studies we have further demonstrated that treatment with individual heavy metals dose-dependently increased the NOX4 protein expression, intracellular ROS production, and decreased the Nrf2, GCLC, and GST protein expression, GST activity, and GSH level in THP-1 monocytes. None of the treatment caused any change in cell viability compared to control. In conclusion, this study suggests that circulatory heavy metals in COPD patients of coal mine site weakened the lung function, decreased the plasma GST activity and GSH level via impairing the NOX4/Nrf2/GCLC/GST signaling pathway in monocytes, which may cause monocyte activation and initiate the COPD pathophysiology.