scholarly journals Myricitrin, a Glycosyloxyflavone in Myrica esculenta Bark Ameliorates Diabetic Nephropathy via Improving Glycemic Status, Reducing Oxidative Stress, and Suppressing Inflammation

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 258
Author(s):  
Tarun K. Dua ◽  
Swarnalata Joardar ◽  
Pratik Chakraborty ◽  
Shovonlal Bhowmick ◽  
Achintya Saha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Therapeutic Potential ◽  
Glycemic Status ◽  
Myrica Esculenta ◽  
Induced Apoptosis ◽  
Type 2 Diabetic

The present study evaluated the therapeutic potential of myricitrin (Myr), a glycosyloxyflavone extracted from Myrica esculenta bark, against diabetic nephropathy. Myr exhibited a significant hypoglycemic effect in high fat-fed and a single low-dose streptozotocin-induced type 2 diabetic (T2D) rats. Myr was found to improve glucose uptake by the skeletal muscle via activating IRS-1/PI3K/Akt/GLUT4 signaling in vitro and in vivo. Myr significantly attenuated high glucose (HG)-induced toxicity in NRK cells and in the kidneys of T2D rats. In this study, hyperglycemia caused nephrotoxicity via endorsing oxidative stress and inflammation resulting in the induction of apoptosis, fibrosis, and inflammatory damages. Myr was found to attenuate oxidative stress via scavenging/neutralizing oxidative radicals and improving endogenous redox defense through Nrf-2 activation in both in vitro and in vivo systems. Myr was also found to attenuate diabetes-triggered renal inflammation via suppressing NF-κB activation. Myr inhibited hyperglycemia-induced apoptosis and fibrosis in renal cells evidenced by the changes in the expressions of the apoptotic and fibrotic factors. The molecular docking predicted the interactions between Myr and different signal proteins. An in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) study predicted the drug-likeness character of Myr. Results suggested the possibility of Myr to be a potential therapeutic agent for diabetic nephropathy in the future.

scholarly journals Autocrine Exosomal Fibulin-1 as a Target of MiR-1269b Induces Epithelial–Mesenchymal Transition in Proximal Tubule in Diabetic Nephropathy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yi-Chun Tsai ◽  
Wei-Wen Hung ◽  
Wei-An Chang ◽  
Ping-Hsun Wu ◽  
Ling-Yu Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Mesenchymal Transition ◽  
Cell Communication ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Mesenchymal Transition ◽  
Type 2 Diabetic

Background: Diabetic nephropathy (DN) is an increasing threat to human health and is regarded to be the leading cause of end-stage renal disease worldwide. Exosomes deliver biomolecule massages and may play a key role in cell communication and the progression of DN.Methods: A cross-disciplinary study, including in vivo, in vitro, and human studies, was conducted to explore the cross-talk within proximal tubular epithelial cells (PTECs) in DN. Exosomal protein from PTECs treated with high glucose (HG) was purified and examined using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Next-generation sequencing (NGS) was utilized to analyze RNAs extracted from PTECs from a type 2 diabetic patient and a normal individual. HK-2 cells were used to assess exosomal protein and its modulation and biofunction in DN. Normal individuals and type 2 diabetic patients were enrolled, and nondiabetic db/m mice and diabetic db/db mice were used to validate the molecular mechanism of exosomes in DN.Results: HG stimulated PTECs to increase Fibulin-1 (FBLN1) expression, and PTECs secreted FBLN1 through exosome delivery, thereby inducing epithelial–mesenchymal transition (EMT) in PTECs. Transcriptome analysis found that FBLN1 expression was modulated by miR-1269b, which was downregulated by HG in HK-2 cells. While transfection of miR-1269b reversed FBLN1-mediated EMT in PTECs, miR-1269b inhibitor modulated the phenotype of PTECs toward mesenchymal type under normal glucose (NG) condition. Most importantly, urinary FBLN1 and exosomal miR-1269b levels were correlated with the severity of kidney injury in type 2 diabetic patients.Conclusion: This study demonstrated the communication within PTECs through exosome transmission in an autocrine pattern. MiR-1269b–FBLN1 epigenetic regulatory network could be a potential therapeutic strategy to prevent the progression of DN.

Gene Regulatory Effect of Pyruvate Kinase M2 is Involved in Renal Inflammation in Type 2 Diabetic Nephropathy

2020 ◽  
Vol 128 (09) ◽  
pp. 599-606 ◽  
Author(s):  
Le Li ◽  
Lei Tang ◽  
Xiaoping Yang ◽  
Ruifang Chen ◽  
Zhen Zhang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Intercellular Adhesion Molecule ◽  
Regulatory Effect ◽  
Intercellular Adhesion Molecule 1 ◽  
Renal Inflammation ◽  
Gene Regulatory ◽  
Type 2 Diabetic

Abstract Background and Aims The inflammation of glomerular endothelial cells induces and promotes the activation of macrophages and contributes to the development of diabetic nephropathy. Thus, this study aimed to investigate the gene regulatory effect and potential role of pyruvate kinase M2 (PKM2) in inflammatory response in diabetic nephropathy. Methods The plasma PKM2 levels of patients with diabetes were evaluated. Eight-week-old mice were divided into three groups (WT, db/db mice, and db/db mice treated with TEPP-46) and raised for 12 weeks. Blood and kidney samples were collected at the end of the experiment. Endothelial cells were stimulated with high glucose with or without TEPP-46. The expression of intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), interleukin 1 beta (IL-1β), phospho-PKM2, PKM2, phospho-STAT3(signal transducer and activator of transcription), STAT3, nuclear factor kappa B (NF-kB), and phospho-NF-kB in vivo and in vitro were determined using Western blot. The activation of macrophages (CD68+CD86+) in the glomeruli was assessed via fluorescent double staining. Moreover, immune endothelial adhesion experiments were performed. Results The plasma PKM2 levels of patients with type 2 diabetes increased. P-PKM2 was up-regulated in vivo and in vitro. TEPP-46 decreased inflammatory cell infiltration and ICAM-1 expression in vivo and in vitro and inhibited the differentiation of macrophages to M1 cells in db/db mice with diabetic nephropathy. PKM2 regulated the phosphorylation of STAT3 and NF-kB. Furthermore, high glucose levels induced the transition from tetramer to dimer and the nuclear translocation of PKM2. Conclusion The gene regulatory effect of PKM2 is involved in renal inflammation in type 2 diabetic nephropathy by promoting the phosphorylation of STAT3 and NF-kB and the expression of intercellular adhesion molecule 1. Thus, the down-regulation of phosphorylated PKM2 may have protective effects against diabetic nephropathy by inhibiting renal inflammation.

Therapeutic Potential of Naringin for Intervertebral Disc Degeneration: Involvement of Autophagy Against Oxidative Stress-Induced Apoptosis in Nucleus Pulposus Cells

2018 ◽  
Vol 46 (07) ◽  
pp. 1561-1580 ◽  
Author(s):  
Zengjie Zhang ◽  
Chenggui Wang ◽  
Jialiang Lin ◽  
Haiming Jin ◽  
Ke Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Therapeutic Potential ◽  
Nucleus Pulposus Cells ◽  
Induced Apoptosis

Intervertebral disc degeneration (IDD) is a major cause of lower back pain, but few efficacious medicines have been developed for IDD. Increased nucleus pulposus cells apoptosis is a dominant pathogenesis of IDD and is considered a therapeutic target. Previously, our group proved that autophagy may protect nucleus pulposus cells against apoptosis. As one of the major bioflavonoids of citrus, naringin activates autophagy. Therefore, we hypothesize that naringin may have therapeutic potential for IDD by activating autophagy in nucleus pulposus cells. In this study, we evaluated the effects of naringin on TBHP-induced oxidative stress in nucleus pulposus cells in vitro as well as in puncture-induced rat IDD model in vivo. Our results showed that naringin could reduce the incidence of oxidative stress-induced apoptosis in nucleus pulposus cells and promoted the expression of autophagy markers LC3-II/I and beclin-1. Meanwhile, inhibition of autophagy by 3-MA may partially reverse the anti-apoptotic effect of naringin, indicating that autophagy was involved in the protective effect of naringin in nucleus pulposus cells. Further study showed that autophagy regulation of naringin may be related to AMPK signaling. Also, we found that naringin treatment can regulate the expression of collagen II, aggrecan and Mmp13 to sustain the extracellular matrix. Furthermore, our in vivo study showed that naringin can ameliorate IDD in puncture-induced rat model. In conclusion, our study suggests that naringin can protect nucleus pulposus cells against apoptosis and ameliorate IDD in vivo, the mechanism may relate to its autophagy regulation.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

scholarly journals Improvements in HOMA indices and pancreatic endocrinal tissues in type 2-diabetic rats by DPP-4 inhibition and antioxidant potential of an ethanol fruit extract of Withania coagulans 

2021 ◽  
Author(s):  
Heera Ram ◽  
Pramod Kumar ◽  
Ashok Purohit ◽  
Priya Kashyap ◽  
Suresh Kumar ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Model Assessment ◽  
Fruit Extract ◽  
Protein Ligands ◽  
Homeostatic Model Assessment ◽  
Docking Protein ◽  
Type 2 Diabetic

Abstract Context: Withania coagulans (Stocks) Dunal fruits are used in the therapeutics of several ailments due to possessing of potent phytoconstituents which is also used traditionally for curing the diabetes. Objective: The present study was assessing the amelioration potential of the phytochemicals of an ethanol fruit extract of Withania coagulans (Stocks) Dunal in the HOMA (Homeostatic model assessment) indices and pancreatic endocrinal tissues by inhibition of DPP-4 and antioxidants activities.Material and methods: The identification of phytoconstituents of the test extract was performed by LCMS. Further, assessments of in-vitro, in-vivo and in-silico were achieved by following standard methods. In-vivo studies were conducted on type-2 diabetic ratsResults: The chosen extract inhibited DPP-4 activity by 63.2% in an in vitro assay as well as significantly inhibit serum DPP-4 levels. Accordingly, the administration of the ethanol fruit extract resulted in a significant (𝑃≤ 0.001) alterations in the lipid profile, antioxidant levels, and HOMA indices. Moreover, pancreatic endocrinal tissues (islet of Langerhans) appeared to have the restoration of normal histoarchitecture as evidenced by increased cellular mass. Molecular docking (Protein - ligands) of identified phytoconstituents with DPP-4 (target enzyme) shown incredibly low binding energy (Kcal/mol) as required for ideal interactions. ADMET analysis of the pharmacokinetics of the identified phytoconstituents indicated an ideal profile as per Lipinski laws. Conclusion: It can be concluded that the phytoconstituents of an ethanol fruit extract of Withania coagulans have the potential to inhibit DPP-4 which result in improved glucose homeostasis and restoration of pancreatic endocrinal tissues in type-2 diabetic rats.

Improvements in HOMA Indices and Pancreatic Endocrinal Tissues in Type -2 Diabetic Rats by DPP-4 Inhibition and Antioxidant Potential of an Ethanol Fruit Extract of Withania Coagulans

2020 ◽  
Author(s):  
Heera Ram ◽  
Pramod Kumar ◽  
Ashok Purohit ◽  
Priya Kashyap ◽  
Suresh Kumar ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Model Assessment ◽  
Fruit Extract ◽  
Withania Coagulans ◽  
Homeostatic Model Assessment ◽  
Docking Protein ◽  
Type 2 Diabetic

Abstract Context: Withania coagulans (Stocks) Dunal fruits are used in the therapeutics of several ailments due to possessing of potent phytoconstituents which is also used traditionally for curing the diabetes. Objective: The present study was assessing the amelioration potential of the phytochemicals of an ethanol fruit extract of Withania coagulans (Stocks) Dunal in the HOMA (Homeostatic model assessment) indices and pancreatic endocrinal tissues by inhibition of DPP-4 and antioxidants activities.Material and methods: The identification of phytoconstituents of phytochemicals of the test extract was performed by LCMS. Further, assessments of in-vitro, in-vivo and in-silico were achieved by following standard methods. In-vivo studies were conducted on type-2 diabetic ratsResults: The chosen extract inhibited DPP-4 activity by 63.2% in an in vitro assay. Accordingly, the administration of the ethanol fruit extract resulted in a significant (𝑃≤ 0.001) alterations in the lipid profile, antioxidant levels, and HOMA indices. Moreover, pancreatic endocrinal tissues (islet of Langerhans) appeared to have the restoration of normal histoarchitecture as evidenced by increased cellular mass. Molecular docking (Protein - ligands) of identified phytoconstituents with DPP-4 (target enzyme) shown incredibly low binding energy (Kcal/mol) as required for ideal interactions. ADMET analysis of the pharmacokinetics of the identified phytoconstituents indicated an ideal profile as per Lipinski laws. Conclusion: It can be concluded that the phytoconstituents of an ethanol fruit extract of Withania coagulans have the potential to inhibit DPP-4 which result in improved glucose homeostasis and restoration of pancreatic endocrinal tissues in type-2 diabetic rats.

scholarly journals Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Kaifeng Li ◽  
Mengen Zhai ◽  
Liqing Jiang ◽  
Fan Song ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Therapeutic Potential ◽  
Ros Generation ◽  
Protective Effects ◽  
Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

scholarly journals In Vitro and In Vivo Inhibitory Effect of Citrus Junos Tanaka Peel Extract against Oxidative Stress-Induced Apoptotic Death of Lung Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1231
Author(s):  
Jin Woo Kim ◽  
Eun Hee Jo ◽  
Ji Eun Moon ◽  
Hanvit Cha ◽  
Moon Han Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Inhibitory Effect ◽  
Lung Cells ◽  
In Vivo Models ◽  
Citrus Junos ◽  
Induced Apoptosis ◽  
Peel Extract

Various stresses derived from both internal and external oxidative environments lead to the excessive production of reactive oxygen species (ROS) causing progressive intracellular oxidative damage and ultimately cell death. The objective of this study was to evaluate the protective effects of Citrus junos Tanaka peel extract (CE) against oxidative-stress induced the apoptosis of lung cells and the associated mechanisms of action using in vitro and in vivo models. The protective effect of CE was evaluated in vitro in NCI-H460 human lung cells exposed to pro-oxidant H2O2. The preventive effect of CE (200 mg/kg/day, 10 days) against pulmonary injuries following acrolein inhalation (10 ppm for 12 h) was investigated using an in vivo mouse model. Herein, we demonstrated the inhibitory effect of CE against the oxidative stress-induced apoptosis of lung cells under a highly oxidative environment. The function of CE is linked with its ability to suppress ROS-dependent, p53-mediated apoptotic signaling. Furthermore, we evaluated the protective role of CE against apoptotic pulmonary injuries associated with the inhalation of acrolein, a ubiquitous and highly oxidizing environmental respiratory pollutant, through the attenuation of oxidative stress. The results indicated that CE exhibits a protective effect against the oxidative stress-induced apoptosis of lung cells in both in vitro and in vivo models.

Myricetin May Provide Protection against Oxidative Stress in Type 2 Diabetic Erythrocytes

2009 ◽  
Vol 64 (9-10) ◽  
pp. 626-630 ◽  
Author(s):  
Kanti Bhooshan Pandey ◽  
Neetu Mishra ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Biological Effects ◽  
Protein Carbonyl ◽  
In Vivo Studies ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Protein Carbonyl Content ◽  
Type 2 Diabetic

Oxidative stress is believed to be a major contributing factor in the development of late complications of diabetes. Many in vitro and in vivo studies have demonstrated that several parameters of red blood cell function and integrity are negatively affected by increased oxidative stress. Plant polyphenols are reported to exert many biological effects due to their antioxidant property. The present study was undertaken to evaluate the antioxidant effect of myricetin on markers of oxidative stress in erythrocytes from type 2 diabetic patients. The study was carried out on blood samples obtained from 23 type 2 diabetic patients and 23 age-matched control subjects. Erythrocytes were subjected to in vitro oxidative stress by incubating with 10-5 M tert-butyl hydroperoxide (t-BHP). Erythrocyte membrane lipid peroxidation and protein oxidation were measured in terms of malondialdehyde (MDA) and protein carbonyl group levels. The results showed an elevated MDA and protein carbonyl content in diabetic erythrocytes which were further increased after incubation with t-BHP. Myricetin at micromolar concentration significantly (p < 0.01) protected an t-BHP-induced increase in levels of oxidative stress parameters of diabetic erythrocytes

scholarly journals Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPKα Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yan-Yan Meng ◽  
Yu-Pei Yuan ◽  
Xin Zhang ◽  
Chun-Yan Kong ◽  
Peng Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Cell Loss ◽  
Protective Role ◽  
Protective Effects ◽  
Morphological Examination ◽  
Heart Injury ◽  
Amp Activated Protein Kinase

Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase α (AMPKα) in vivo and in vitro. Moreover, inhibition of AMPKα could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPKα. GE has therapeutic potential for the treatment of DOX cardiotoxicity.

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