scholarly journals Resveratrol increases nucleus pulposus matrix synthesis through activating the PI3K/Akt signaling pathway under mechanical compression in a disc organ culture

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Xiaorui Han ◽  
Xiaoming Leng ◽  
Man Zhao ◽  
Mei Wu ◽  
Amei Chen ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Mechanical Load ◽  
Staining Intensity ◽  
Akt Pathway ◽  
Dependent Manner ◽  
Mechanical Compression ◽  
Matrix Synthesis ◽  
High Magnitude ◽  
Collagen Ii ◽  
Dose Dependent

Disc nucleus pulposus (NP) matrix homeostasis is important for normal disc function. Mechanical overloading seriously decreases matrix synthesis and increases matrix degradation. The present study aims to investigate the effects of resveratrol on disc NP matrix homeostasis under a relatively high-magnitude mechanical compression and the potential mechanism underlying this process. Porcine discs were perfusion-cultured and subjected to a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days in a mechanically active bioreactor. The non-compressed discs were used as controls. Resveratrol was added along with culture medium to observe the effects of resveratrol on NP matrix synthesis under mechanical load respectively. NP matrix synthesis was evaluated by histology, biochemical content (glycosaminoglycan (GAG) and hydroxyproline (HYP)), and expression of matrix macromolecules (aggrecan and collagen II). Results showed that this high-magnitude mechanical compression significantly decreased NP matrix content, indicated by the decreased staining intensity of Alcian Blue and biochemical content (GAG and HYP), and the down-regulated expression of NP matrix macromolecules (aggrecan and collagen II). Further analysis indicated that resveratrol partly stimulated NP matrix synthesis and increased activity of the PI3K/Akt pathway in a dose-dependent manner under mechanical compression. Together, resveratrol is beneficial for disc NP matrix synthesis under mechanical overloading, and the activation of the PI3K/Akt pathway may participate in this regulatory process. Resveratrol may be promising to regenerate mechanical overloading-induced disc degeneration.

scholarly journals Resveratrol attenuates mechanical compression-induced nucleus pulposus cell apoptosis through regulating the ERK1/2 signaling pathway in a disc organ culture

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Zhiwen Zhang ◽  
Feng Wen ◽  
Chengjian He ◽  
Jun Yu
Keyword(s):  
Organ Culture ◽  
Nucleus Pulposus ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Dependent Manner ◽  
Protective Effects ◽  
Mechanical Compression ◽  
High Magnitude ◽  
Regulated Expression ◽  
Dose Dependent

Background: Nucleus pulposus (NP) cell apoptosis is a typical feature within the degenerative disc. High magnitude compression significantly promotes NP cell apoptosis. Several studies have indicated that resveratrol has protective effects on disc cell’s normal biology. Objective: The present study aims to investigate whether resveratrol can attenuate mechanical overloading-induced NP cell apoptosis in a disc organ culture. Methods: Isolated porcine discs were cultured in culture chambers of a mechanically active perfusion bioreactor and subjected to a relatively high magnitude compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days. Different concentrations (50 and 100 μM) of resveratrol were added into the culture medium to observe the protective effects of resveratrol against NP cell apoptosis under mechanical compression. The noncompressed discs were used as controls. Results: Similar with the previous studies, this high magnitude compression significantly promoted NP cell apoptosis, reflected by the increased number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining-positive NP cells and enzyme (caspase-9 and caspase-3) activity, the up-regulated expression of proapoptotic molecules (Bax and caspase-3/cleaved caspase-3), and down-regulated expression of antiapoptotic molecule (Bcl-2). However, resveratrol partly attenuated NP cell apoptosis under this high magnitude compression in a dose-dependent manner. Additionally, though the ERK1/2 pathway was significantly activated in the mechanical compression group, resveratrol partly attenuated activation of the ERK1/2 pathway under mechanical compression in a dose-dependent manner. Conclusion: Resveratrol attenuates mechanical overloading-induced NP cell apoptosis in a dose-dependent manner, and inhibiting activation of the ERK1/2 pathway may be one potential mechanism behind this regulatory process.

scholarly journals Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

2018 ◽  
Vol 46 (2) ◽  
pp. 482-491 ◽  
Author(s):  
Yichun Xu ◽  
Hui Yao ◽  
Pei Li ◽  
Wenbin Xu ◽  
Junbin Zhang ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Dynamic Compression ◽  
Akt Pathway ◽  
Bioreactor Culture ◽  
Nucleus Pulposus Cells ◽  
Matrix Synthesis ◽  
Static Compression ◽  
Matrix Deposition ◽  
The Matrix

Background/Aims: An adequate matrix production of nucleus pulposus (NP) cells is an important tissue engineering-based strategy to regenerate degenerative discs. Here, we mainly aimed to investigate the effects and mechanism of mechanical compression (i.e., static compression vs. dynamic compression) on the matrix synthesis of three-dimensional (3D) cultured NP cells in vitro. Methods: Rat NP cells seeded on small intestinal submucosa (SIS) cryogel scaffolds were cultured in the chambers of a self-developed, mechanically active bioreactor for 10 days. Meanwhile, the NP cells were subjected to compression (static compression or dynamic compression at a 10% scaffold deformation) for 6 hours once per day. Unloaded NP cells were used as controls. The cellular phenotype and matrix biosynthesis of NP cells were investigated by real-time PCR and Western blotting assays. Lentivirus-mediated N-cadherin (N-CDH) knockdown and an inhibitor, LY294002, were used to further investigate the role of N-CDH and the PI3K/Akt pathway in this process. Results: Dynamic compression better maintained the expression of cell-specific markers (keratin-19, FOXF1 and PAX1) and matrix macromolecules (aggrecan and collagen II), as well as N-CDH expression and the activity of the PI3K/Akt pathway, in the 3D-cultured NP cells compared with those expression levels and activity in the cells grown under static compression. Further analysis showed that the N-CDH knockdown significantly down-regulated the expression of NP cell-specific markers and matrix macromolecules and inhibited the activation of the PI3K/Akt pathway under dynamic compression. However, inhibition of the PI3K/Akt pathway had no effects on N-CDH expression but down-regulated the expression of NP cell-specific markers and matrix macromolecules under dynamic compression. Conclusion: Dynamic compression increases the matrix synthesis of 3D-cultured NP cells compared with that of the cells under static compression, and the N-CDH-PI3K/Akt pathway is involved in this regulatory process. This study provides a promising strategy to promote the matrix deposition of tissue-engineered NP tissue in vitro prior to clinical transplantation.

scholarly journals N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression

2017 ◽  
Vol 43 (6) ◽  
pp. 2327-2337 ◽  
Author(s):  
Zhenyu Wang ◽  
Jiali Leng ◽  
Yuguang Zhao ◽  
Dehai Yu ◽  
Feng Xu ◽  
...  
Keyword(s):  
Cell Viability ◽  
Nucleus Pulposus ◽  
Cell Biology ◽  
Mechanical Load ◽  
Cell Phenotype ◽  
Nucleus Pulposus Cells ◽  
Keratin 19 ◽  
High Magnitude ◽  
And Control

Background/Aims: Mechanical load can regulate disc nucleus pulposus (NP) biology in terms of cell viability, matrix homeostasis and cell phenotype. N-cadherin (N-CDH) is a molecular marker of NP cells. This study investigated the role of N-CDH in maintaining NP cell phenotype, NP matrix synthesis and NP cell viability under high-magnitude compression. Methods: Rat NP cells seeded on scaffolds were perfusion-cultured using a self-developed perfusion bioreactor for 5 days. NP cell biology in terms of cell apoptosis, matrix biosynthesis and cell phenotype was studied after the cells were subjected to different compressive magnitudes (low- and high-magnitudes: 2% and 20% compressive deformation, respectively). Non-loaded NP cells were used as controls. Lentivirus-mediated N-CDH overexpression was used to further investigate the role of N-CDH under high-magnitude compression. Results: The 20% deformation compression condition significantly decreased N-CDH expression compared with the 2% deformation compression and control conditions. Meanwhile, 20% deformation compression increased the number of apoptotic NP cells, up-regulated the expression of Bax and cleaved-caspase-3 and down-regulated the expression of Bcl-2, matrix macromolecules (aggrecan and collagen II) and NP cell markers (glypican-3, CAXII and keratin-19) compared with 2% deformation compression. Additionally, N-CDH overexpression attenuated the effects of 20% deformation compression on NP cell biology in relation to the designated parameters. Conclusion: N-CDH helps to restore the cell viability, matrix biosynthesis and cellular phenotype of NP cells under high-magnitude compression.

PAEDERUS ALFIERI EXTRACT INDUCES APOPTOSIS IN HUMAN MYELOID LEUKEMIA K562 CELLS

2016 ◽  
Vol 10 (1) ◽  
pp. 72
Author(s):  
Amer Mohamed ◽  
Osama Rakha
Keyword(s):  
Myeloid Leukemia ◽  
Caspase 3 ◽  
Insect Pests ◽  
Flow Cytometric Analysis ◽  
K562 Cells ◽  
Akt Pathway ◽  
Dependent Manner ◽  
Proliferative Effect ◽  
Induced Apoptosis ◽  
Dose Dependent

ABSTRACTObjective: The rove beetle Paederus alfieri Koch. (Coleoptera: Staphylinidae) is well-known among natural enemies in Egypt as an important predatorof agricultural insect pests, it used as an essential agent in the integrated pest management programs. Recent studies have revealed that Paederus mayhave anti-proliferative effect; however, its mechanisms remain unclear. The aim of the present study is to investigate the anticancer effect of P. alfieriextract (PAE) on K562 human myeloid leukemia cancer cells and elucidation of its mechanism.Methods: Human myeloid leukemia K562 cells were treated with PAE at different concentrations. Cell proliferation was measured using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was evaluated using flow cytometry analysis. The expressions ofBcl-2, Bax, active caspase-3, t-Akt, and p-Akt were evaluated by western blotting.Results: PAE has a dose-dependent antiproliferative effect against K562 cells. The half maximal inhibitory concentration was estimated as212±2.3 ng/ml. Flow cytometric analysis showed that PAE induces apoptosis in a dose-dependent manner in K562 cells. We also investigated themolecular mechanism of PAE-induced apoptosis. PAE downregulated Bcl-2 and upregulated Bax and cleaved caspase-3 proteins. Furthermore, thelevels of p-Akt are dose-dependently decreased in response to PAE, whereas the total Akt protein levels remained constant during PAE treatment.Conclusion: Taken together PAE-induced apoptosis in human myeloid leukemia K562 cells by modulating PI3K/Akt pathway. Our findings suggestthat may be PAE is a good extract for developing anticancer drugs for human myeloid leukemia cancer treatment.Keywords: Paederus alfieri, Pederin, K562, Apoptosis, PI3K/Akt pathway.

The Anti-inflammatory Effects of Lignan Glycosides from Cistanche tubulosa stems on LPS/IFN-γ-induced RAW264.7 Macrophage Cells via PI3K/AKT Pathway

2020 ◽  
Vol 21 ◽  
Author(s):  
Jinhan Guo ◽  
Shuming Tang ◽  
Yuyang Miao ◽  
Lanlan Ge ◽  
Junfa Xu ◽  
...  
Keyword(s):  
Raw264.7 Cells ◽  
Akt Pathway ◽  
No Production ◽  
Dependent Manner ◽  
Ifn Γ ◽  
Cox 2 ◽  
Cistanche Tubulosa ◽  
Anti Inflammatory ◽  
Lignan Glycosides ◽  
Dose Dependent

Background: Cistanche tubulosa is a tonic in traditional Chinese medicines and has a broad spectrum of biological activity, including anti-inflammatory. However, its anti-inflammatory major constituents of C. tubulosa and their underlying mechanisms are still unknown. Objective: The aim of the current study was to explore the separation and structural characterization of lignan glycosides from C. tubulosa (Schenk) Wight., their anti-inflammatory activity and underlying mechanism. Materials and Methods: Fractionation and isolation of the 85% EtOH extract of C. tubulosa (Schenk) Wight. were carried out and the primary ingredients lignan glycosides (1-6) were structurally characterized. CCK8 methods were used to evaluate the cytotoxic effect of lignan glycosides (1-6). Effects of lignan glycosides (1-6) on NO production in LPS/IFN-γ-induced RAW264.7 macrophages cells were measured using Griess reagent by reaction with nitrite. The mRNA expression levels of iNOS, COX-2, IL-1β, IL-6, TNF-a, and TGF-β treated RAW264.7 cells with various concentrations (0, 25 and 50 μg/ml) of lignan glycosides (1, 4) in the presence of LPS (10 ng/ml) and IFN-γ (20 ng/ml) for 24 h were analyzed by quantitative RT-PCR. Also the protein expressions of iNOS, COX-2, PI3K, AKT, p-AKT and β-actin were determined using Western blot analysis. A molecular docking study was performed to investigate the interactions between the lignan glycosides and the PI3K using Autodock vina 1.1.2 package. Results: Six lignan glycosides (1-6) were isolated from stems of C. tubulosa. Among them, (+)-pinoresinol-4-O-β-D-glucopyranosyl- (1→6)-β-D- glucopyranoside (5) and eleutheroside E (6) were firstly isolated from C. tubulosa. Of these lignans, 1 and 4 exhibited pronounced inhibitions on NO production with the values of 33.63 ± 4.78 and 39.28 ± 5.52 % at 50 μg/ml, respectively. Additionally, LPS/IFN-γ-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-a (TNF-a) was significantly suppressed by pre-treatment of 1 and 4 in a dose-dependent manner. While 1 and 4 increased the mRNA levels of anti-inflammatory cytokines (TGF-β). Furthermore, 1 and 4 significantly inhibited the protein levels of PI3K and p-AKT in a dose-dependent manner. Conclusion: Taken together, these results suggest that 1 and 4 play an important role in the attenuation of LPS/IFN-γ-induced inflammatory responses in RAW264.7 cells and that the mechanisms involve down-regulation of the PI3K/AKT pathway.

The protective effect of ligustrazine on rats with cerebral ischemia–reperfusion injury via activating PI3K/Akt pathway

2019 ◽  
Vol 38 (10) ◽  
pp. 1168-1177 ◽  
Author(s):  
Y Ding ◽  
J Du ◽  
F Cui ◽  
L Chen ◽  
K Li
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Ischemia Reperfusion ◽  
Pi3k Inhibitor ◽  
Akt Pathway ◽  
Control Group ◽  
Dependent Manner ◽  
Cerebral Ischemia Reperfusion ◽  
Dose Dependent

The study was to investigate the effects of ligustrazine on rats with cerebral ischemia–reperfusion (I/R) injury and to explore the potential mechanism. Transient focal cerebral ischemia Wistar rat model was established through middle cerebral artery occlusion. The cerebral I/R injury rats were treated with intraperitoneal injection of ligustrazine (1, 3, and 10 mg/kg). Human amniotic epithelial cells (HAECs) were treated with ligustrazine (1, 10, 100 μM) and PI3K inhibitor wortmannin (100 μM), following oxygen–glucose deprivation (OGD) treatment. The expression levels of protein kinase B (PKB or AKT), phospho-Akt (p-Akt), endothelial nitric oxide synthase (eNOS), and phosphor-eNOS (p-eNOS) in HAECs and brains of rats were measured by Western blot. The levels of nitric oxide (NO) in HAECs were measured by Griess method using NO2−/NO3− Assay Kit. Infarct volume and neurological deficits were evaluated 24 h after reperfusion. The levels of NO, p-Akt/Akt, and p-eNOS/eNOS in HAECs were significantly reduced after OGD, but ligustrazine treatment increased the levels of those factors in a dose-dependent manner, while those increases were reversed by PI3K inhibitor wortmannin. Similarly, p-Akt/Akt and p-eNOS/eNOS in brain tissue of rats with I/R were significantly reduced compared with control group ( p < 0.05), but ligustrazine treatment increased the levels of p-Akt and p-eNOS in a dose-dependent manner ( p < 0.05), while those increases were also reversed by using wortmannin. Ligustrazine also improved the damage of rat brain tissue caused by I/R, but wortmannin reversed the improvement. Ligustrazine plays a neuroprotective role in rats with cerebral I/R injury through the activation of PI3K/Akt pathway.

Eel insulin: isolation, characterization and stimulatory actions on [35S]sulphate and [3H]thymidine uptake in the branchial cartilage of the eel in vitro

1992 ◽  
Vol 133 (2) ◽  
pp. 221-230 ◽  
Author(s):  
C. Duan ◽  
T. Noso ◽  
S. Moriyama ◽  
H. Kawauchi ◽  
T. Hirano
Keyword(s):  
Bovine Insulin ◽  
Cartilage Matrix ◽  
Common Mechanism ◽  
Thymidine Uptake ◽  
Dependent Manner ◽  
Matrix Synthesis ◽  
Sulphate Uptake ◽  
Igf I ◽  
Dose Dependent

ABSTRACT Our previous studies have shown that mammalian and salmon insulins stimulate sulphate uptake by cultured eel cartilage, suggesting the possible involvement of insulin in the regulation of cartilage matrix synthesis. In the present study, homologous eel insulin was isolated and characterized, and its effects on cartilage matrix synthesis and DNA synthesis were examined in vitro. Insulin was extracted from eel pancreas with acid–ethanol, and subsequently purified by isoelectric precipitation at pH 5·3, gel filtration on Sephadex G-50, and reversed-phase high-performance liquid chromatography. The amino acid composition and complete sequence (50 residues) of eel insulin revealed high homology to teleostean and mammalian insulins. The isolated eel insulin produced a more pronounced and longer lasting hypoglycaemic effect than bovine insulin in the eel. Homologous eel insulin, like bovine insulin-like growth factor (IGF-I) and insulin, stimulated sulphate uptake by cultured eel cartilage in a dose-dependent manner (16–1000 ng/ml). Combination experiments using maximal concentrations of bovine IGF-I (250 ng/ml) and increasing amounts of eel insulin (10–250 ng/ml) showed no additive effects of insulin on sulphate uptake, suggesting that insulin and IGF-I may share a common mechanism(s) of action. Eel insulin and bovine IGF-I also enhanced thymidine incorporation by eel cartilage in a dose-dependent manner (4–1000 ng/ml); eel insulin was equipotent with bovine IGF-I. These results suggest that insulin, like IGF-I, may exert direct growth-promoting actions in branchial cartilage of the eel. Journal of Endocrinology (1992) 133, 221–230

scholarly journals Ginsenoside Rg2 Attenuates Doxorubicin-induced Cardiomyocyte Apoptosis via PI3K/Akt Pathway

2021 ◽  
Author(s):  
Boyong Qiu ◽  
Meijiao Mao ◽  
Shuai Zhang ◽  
Bing Deng ◽  
Lin Shen ◽  
...  
Keyword(s):  
Cardiomyocyte Apoptosis ◽  
Cell Counting ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Akt Pathway ◽  
Dependent Manner ◽  
P53 Expression ◽  
Akt Phosphorylation ◽  
Underlying Mechanisms ◽  
Dose Dependent ◽  
Important Drug

Abstract Doxorubicin (DOX) is an important drug for cancer therapy; however, its use is limited by its cardiotoxicity. Ginsenoside Rg2 is extracted from Panax ginseng, which is believed to have cardioprotective properties. However, to date, there have been no reports on whether ginsenoside Rg2 could protect cardiomyocytes against DOX. In this study, we investigated the action and underlying mechanisms of ginsenoside Rg2 upon DOX treatment. This study aimed to explore the cardioprotective effects of ginsenoside Rg2 against DOX treatment. Cell Counting kit-8 was used to determine cell viability and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining was used to detect apoptotic cells. Western blotting was used to investigate the relevant pathways. LY294002 (LY294), a PI3K inhibitor, was used in this study. We found that ginsenoside Rg2 significantly (P < 0.01) neutralized cardiomyocyte apoptosis induced by DOX in a dose-dependent manner, which was blocked by LY294. Moreover, ginsenoside Rg2 upregulated Akt phosphorylation through the PI3K/Akt pathway and inhibited p53 expression. Taken together, Ginsenoside Rg2 attenuates DOX-induced cardiomyocyte apoptosis via the PI3K/Akt pathway.

scholarly journals Nucleus pulposus cell senescence is alleviated by resveratrol through regulating the ROS/NF-κB pathway under high-magnitude compression

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Yanhai Jiang ◽  
Guozhang Dong ◽  
Yeliang Song
Keyword(s):  
Nucleus Pulposus ◽  
Bone Matrix ◽  
Nucleus Pulposus Cell ◽  
Cell Senescence ◽  
Ros Generation ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
High Magnitude

Mechanical overloading is a risk factor of disc degeneration. Studies have demonstrated that resveratrol helps to maintain the disc cell’s healthy biology. The present study aims to investigate whether resveratrol can suppress mechanical overloading-induced nucleus pulposus (NP) cell senescence in vitro and the potential mechanism. The isolated rat NP cells were seeded in the decalcified bone matrix (DBM) and cultured under non-compression (control) and compression (20% deformation, 1.0 Hz, 6 h/day) for 5 days using the mechanically active bioreactor. The resveratrol (30 and 60 μM) was added into the culture medium of the compression group to investigate its protective effects against the NP cell senescence. NP cell senescence was evaluated by cell proliferation, cell cycle, senescence-associated β-galactosidase (SA-β-Gal) activity, telomerase (TE) activity, and gene expression of the senescence markers (p16 and p53). Additionally, the reactive oxygen species (ROS) content and activity of the NF-κB pathway were also analyzed. Compared with the non-compression group, the high-magnitude compression significantly promoted NP cell senescence, increased ROS generation and activity of the NF-κB pathway. However, resveratrol partly attenuated NP cell senescence, decreased ROS generation and activity of the NF-κB pathway in a concentration-dependent manner under mechanical compression. Resveratrol can alleviate mechanical overloading-induced NP cell senescence through regulating the ROS/NF-κB pathway. The present study provides that resveratrol may be a potential drug for retarding mechanical overloading-induced NP cell senescence.

scholarly journals Protective Effects of Astragaloside IV on Uric Acid-Induced Pancreatic β-Cell Injury through PI3K/AKT Pathway Activation

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Zhenhuan Jiang ◽  
Gang Wang ◽  
Lingling Meng ◽  
Yunzhao Tang ◽  
Min Yang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Insulin Secretion ◽  
Akt Pathway ◽  
Dependent Manner ◽  
Protective Effects ◽  
Pancreatic Β Cell ◽  
Astragaloside Iv ◽  
Β Cell ◽  
Min6 Cells ◽  
Dose Dependent

Background. Elevated uric acid (UA) has been found to damage pancreatic β-cell, promote oxidative stress, and cause insulin resistance in type 2 diabetes (T2D). Astragaloside IV (AS-IV), a major active monomer extracted from Astragalus membranaceus (Fisch.) Bunge. which belongs to TRIB. Galegeae (Br.) Torrey et Gray, Papilionaceae, exhibits various activities in a pathophysiological environment and has been widely employed to treat diseases. However, the effects of AS-IV on UA-induced pancreatic β-cell damage need to be investigated and the associating mechanism needs to be elucidated. This study was designed to determine the protective effects and underlying mechanism of AS-IV on UA-induced pancreatic β-cell dysfunction in T2D. Methods. UA-treated Min6 cells were exposed to AS-IV or wortmannin. Thereafter, the 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide (MTT) assay and flow cytometry were employed to determine the effect of AS-IV on cell proliferation and apoptosis, respectively. Insulin secretion was evaluated using the glucose-stimulated insulin secretion (GSIS) assay. Finally, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to determine the effect of AS-IV on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in UA-treated cells. Results. AS-IV had no cytotoxic effects on Min6 cells. UA significantly suppressed Min6 cell growth, promoted cell apoptosis, and enhanced caspase-3 activity; however, AS-IV abolished these effects in a dose-dependent manner. Further, decreased insulin secretion was found in UA-treated Min6 cells compared to control cells, and the production of insulin was enhanced by AS-IV in a dose-dependent manner. AS-IV significantly increased phosphorylated (p)-AKT expression and the ratio of p-AKT/AKT in Min6 cells exposed to UA. No evident change in AKT mRNA level was found in the different groups. However, the effects of AS-IV on UA-stimulated Min6 cells were reversed by 100 nM wortmannin. Conclusion. Collectively, our data suggest that AS-IV protected pancreatic β-cells from UA-treated dysfunction by activating the PI3K/AKT pathway. Such findings suggest that AS-IV may be an efficient natural agent against T2D.

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