Optimization of Jiuzao protein hydrolysis conditions and antioxidant activity in vivo of Jiuzao tetrapeptide Asp-Arg-Glu-Leu by elevating Nrf2/Keap1-p38/PI3K-MafK signaling pathway

2021 ◽  
Author(s):  
Yunsong Jiang ◽  
Rui Wang ◽  
Zhongtian Yin ◽  
Jinyuan Sun ◽  
Bowen Wang ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Signaling Pathway ◽  
Hepg2 Cell ◽  
Cell Model ◽  
Protein Hydrolysates ◽  
Protein Hydrolysis ◽  
Alkaline Proteinase ◽  
Hydrolysis Conditions

Tetrapeptide Asp-Arg-Glu-Leu (DREL) was isolated from Jiuzao protein hydrolysates (JPHs) by alkaline proteinase (AP) and exhibited antioxidant activity by HepG2 cell model in the previous study. In this study, hydrolysis...

scholarly journals Dangshen Erling Decoction Ameliorates Myocardial Hypertrophy via Inhibiting Myocardial Inflammation

2022 ◽  
Vol 12 ◽  
Author(s):  
Yigang Zhong ◽  
Liuying Chen ◽  
Miaofu Li ◽  
Lian Chen ◽  
Yufeng Qian ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cardiac Tissue ◽  
Myocardial Hypertrophy ◽  
Cell Model ◽  
H9c2 Cell ◽  
Myocardial Inflammation ◽  
Cross Sectional ◽  
Tnf Α

Myocardial hypertrophy plays an essential role in the structural remodeling of the heart and the progression to heart failure (HF). There is an urgent need to understand the mechanisms underlying cardiac hypertrophy and to develop treatments for early intervention. Dangshen Erling decoction (DSELD) is a clinically used formula in Chinese medicine for treating coronary heart disease in patients with HF. However, the mechanism by which DSELD produces its cardioprotective effects remains largely unknown. This study explored the effects of DSELD on myocardial hypotrophy both in vitro and in vivo. In vitro studies indicated that DSELD significantly (p < 0.05) reduced the cross-sectional area of the myocardium and reduced elevated lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels in the induced H9C2 cell model to study inflammation. In vivo experiments revealed that DSELD restores cardiac function and significantly reduces myocardial fibrosis in isoproterenol (ISO)-induced HF mouse model (p < 0.05). In addition, DSELD downregulated the expression of several inflammatory cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), IL-1α, IL-1β, IL-3, IL-5, IL-7, IL-12, IL-13, and TNF-α in HF (p < 0.05). Further analysis of the cardiac tissue demonstrated that DSELD produces its anti-inflammatory effects via the Toll-like receptor (TLR)4 signaling pathway. The expression of TLR4 downstream proteins such as matrix metalloproteinase-9 (MMP9) and myeloid differentiation factor-88 (MyD88) was among the regulated targets. In conclusion, these observations suggest that DSELD exerts antihypertrophic effects by alleviating the inflammatory injury via the TLR4 signaling pathway in HF and thus holds promising therapeutic potentials.

scholarly journals Advance on anti-diabetic effects of protein hydrolysates and peptides derived from cereals and pseudocereals

2020 ◽  
Vol 189 ◽  
pp. 02030
Author(s):  
Weijing Wu ◽  
Wen Xie ◽  
Qianglai Tan ◽  
Lanlan Wu ◽  
Shanshan Zhu ◽  
...  
Keyword(s):  
Dietary Protein ◽  
Bioactive Peptides ◽  
Cell Model ◽  
Digestive Enzyme ◽  
Protein Hydrolysates ◽  
Staple Food ◽  
Elevated Blood ◽  
Global Public Health

Diabetes is a complex and heterogeneous disorder disease with elevated blood glucose, which is one of the most serious global public health problems. Cereals and pseudocereals, as staple food, are major sources of dietary protein. Cereal and pseudocereal proteins are potential sources of food-derived bioactive peptides and proposed to prevent and ameliorate diabetes. According to recent researches, this review summaries the isolation, purification and analysis of anti-diabetic protein hydrolysates and peptides from cereals and pseudocereals. In addition, their anti-diabetic activities and mechanisms were reviewed by in vitro inhibition of carbohydrate digestive enzyme and dipeptidyl peptidase-IV, in vivo hypoglycaemic effects, and glucose homeostasis in cell model.

Circ-Ctnnb1 regulates neuronal injury in spinal cord injury through Wnt/β-catenin signaling pathway

2021 ◽  
Author(s):  
Jialong Qi ◽  
Tao Wang ◽  
Zhidong Zhang ◽  
Zongsheng Yin ◽  
Yiming Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Rat Model ◽  
Cell Model ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Cord Injury

Study design: Spinal cord injury (SCI) rat model and cell model were established for in vivo and in vitro experiments. Functional assays were utilized to explore the role of the circRNAs derived from catenin beta 1 (mmu_circ_0001859, circ-Ctnnb1 herein) in regulating neuronal cell viability and apoptosis. Bioinformatics analysis and mechanism experiments were conducted to assess the underlying molecular mechanism of circ-Ctnnb1. Objective: We aimed to probe into the biological function of circ-Ctnnb1 in neuronal cells of SCI. Methods: The rat model of SCI and hypoxia-induced cell model were constructed to examine circ-Ctnnb1 expression in SCI through quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). Basso, Beattie and Bresnahan (BBB) score was utilized for evaluating the neurological function. Terminal-deoxynucleoitidyl Transferase Mediated Nick End labeling (TUNEL) assays were performed to assess the apoptosis of neuronal cells. RNase R and Actinomycin D (ActD) were used to treat cells to evaluate the stability of circ-Ctnnb1. Results: Circ-Ctnnb1 was highly expressed in SCI rat models and hypoxia-induced neuronal cells, and its deletion elevated the apoptosis rate of hypoxia-induced neuronal cells. Furthermore, circ-Ctnnb1 activated the Wnt/β-catenin signaling pathway via sponging mircoRNA-205-5p (miR-205-5p) to up-regulate Ctnnb1 and Wnt family member 2B (Wnt2b). Conclusion: Circ-Ctnnb1 promotes SCI through regulating Wnt/β-catenin signaling via modulating the miR-205-5p/Ctnnb1/Wnt2b axis.

scholarly journals Exenatide Attenuates Non-Alcoholic Steatohepatitis by Inhibiting the Pyroptosis Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Liu ◽  
Da-Wei Wang ◽  
Dan Wang ◽  
Bin-Hong Duan ◽  
Hong-Yu Kuang
Keyword(s):  
Type 2 Diabetes ◽  
Signaling Pathway ◽  
Leptin Receptor ◽  
Cell Model ◽  
Clinical Use ◽  
Male Mice ◽  
Alcoholic Steatohepatitis

Background/AimsExenatide is a glucagon-like polypeptide-1 analog, whose main clinical use is to treat type 2 diabetes. However, the mechanism of exenatide in mitigating non-alcoholic steatohepatitis (NASH) remains unclear. This study aimed to investigate the in vitro and in vivo effect of exenatide on NASH.MethodsLeptin receptor-deficient C57BL/KsJ- db/db male mice were fed with methionine-choline-deficient (MCD) diet for 4 weeks to induce NASH, while oleic acid/LPS-treated HepG2 cells were used as an in vitro cell model. Exenatide (20 µg/kg/day, subcutaneous) and specific exenatide inhibitors (20 µg/kg/day, intraperitoneal) were used to determine the effects of exenatide on NASH.ResultsExenatide treatment inhibited the pyroptosis signaling pathway to attenuate NASH.ConclusionTo the best of our knowledge, this report provides the first evidence showing that exenatide attenuated NASH by inhibiting the pyroptosis signaling pathway. Exenatide thus has important pathophysiological functions in NASH and may represent a useful new therapeutic target.

scholarly journals Hei-Gu-Teng Zhuifenghuoluo Granule Modulates IL-12 Signal Pathway to Inhibit the Inflammatory Response in Rheumatoid Arthritis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Kang Zheng ◽  
Zexu Chen ◽  
Wen Sun ◽  
Bin Liu ◽  
Danping Fan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Bioinformatics Analysis ◽  
Cell Model ◽  
Mice Model ◽  
Sinomenium Acutum ◽  
Systemic Inflammatory Disease ◽  
Anti Inflammatory

Rheumatoid arthritis (RA) is a type of chronic systemic inflammatory disease; it has a very complicated pathogenesis, and multiple pathological changes are implicated. Traditional Chinese medicine (TCM) like Tripterygium wilfordii Hook. F. or Sinomenium acutum (Thunb.) Rehd et Wils. has been extensively used for centuries in the treatment of arthritic diseases and been reported effective for relieving the severity of RA. Hei-Gu-Teng Zhuifenghuoluo granule (HGT) which contains Periploca forrestii Schltr., Sinomenium acutum (Thunb.) Rehd et Wils., and Lysimachia paridiformis Franch. var. stenophylla Franch. was a representative natural rattan herb formula for the treatment of RA in China, but the mechanism has not been elucidated. This study aimed at exploring the mechanism of HGT on RA using the bioinformatics analysis with in vivo and in vitro experiment validation. The potential action mechanism was first investigated by bioinformatics analysis via Ingenuity Pathway Analysis (IPA) software. After that, we use experimental validation such as collagen-induced arthritis (CIA) mice model in vivo and U937 cell model in vitro. The bioinformatics results suggested that HGT may have anti-inflammatory characteristic on RA and IL-12 signaling pathway could be the potential key trigger. In vivo experiments demonstrated that HGT ameliorated the symptoms in CIA mice and decreased the production of inflammatory cytokines in both mice ankle joints and serum. Furthermore, HGT effectively inhibited the activation of IL-12R and STAT4 on IL-12 signaling pathway. In vitro experiments showed that HGT inhibited the production of IL-12R and STAT4 induced by IL-12 in lipopolysaccharide- (LPS-) stimulated U937 cells. Moreover, IL-12R knockdown was able to interfere with the inhibition effects of HGT on the production of these cytokines. Our results confirmed the anti-inflammatory property of HGT, which was attributed to its inhibition on IL-12 signaling pathway.

Oxidative Stress Reducing Osteogenesis Reversed by Curcumin via NF-κB Signaling and Had a Role in Anti-Osteoporosis

2021 ◽  
Author(s):  
Xu JiaQiang ◽  
Ran Gao ◽  
Wen Liang ◽  
ChangJian Wu ◽  
FangLing Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Cell Model ◽  
Antioxidant Properties ◽  
Calcium Content ◽  
Dependent Manner ◽  
Osteoporosis Prevention ◽  
High Concentration ◽  
Mineral Density

Abstract Objective: Curcumin has good anti-inflammatory and antioxidant properties, and whether it can resist osteoporosis through oxidative stress pathway in a dose-dependent manner.Method: we used an oxidative stress cell model by culture cells with hydrogen peroxide (H2O2), cells were osteogenic differentiation after treated with H2O2，different concentration curcumin were added during differentiation, then measured the early and late osteogenic index, and detected the potential signaling pathway involved. In addition, we employed rat OVX model treated with curcumin to confirm the protection of the anti-oxidant.Result: Low concentrations of curcumin (1-10μM) promoted the proliferation of MC3T3-E1 cells, improved alkaline phosphatase (ALP) activity, elevated calcium content against oxidative stress induced by H2O2, but high concentration (20 μM) failed, moreover, curcumin diminished supernatant receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 expression, inhibited the intracellular ROS triggered by H2O2, Notably, curcumin exerted protection by blocking the NF-κB signaling pathway. The curcumin administered for 12 weeks partially reversed the raito of blood malondialdehyde (MDA) and glutathione (GSH) activity in ovariectomized (OVX) rat in vivo. It also increased the bone mineral density (BMD) and improved the micro-architecture of trabecular bones. Conclusion: curcumin exerted protection on osteoporosis, the effect linked to a reduction of oxidative stress and bone resorbing cytokine, This study suggests that curcumin might be a candidate for osteoporosis prevention and the low concentration exerted obviously protection.

scholarly journals Ameliorative Effects of Osthole on Experimental Renal Fibrosis in vivo and in vitro by Inhibiting IL-11/ERK1/2 Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Fan Wu ◽  
Yan Zhao ◽  
Qingqing Shao ◽  
Ke Fang ◽  
Ruolan Dong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Cell Model ◽  
Smooth Muscle Actin ◽  
Collagen I ◽  
Mrna Levels ◽  
Smad Signaling ◽  
Tgf Β1

Objectives: Natural product, osthole, has been proven to have a protective effect on organ fibrosis, including renal fibrosis. All of these studies are mainly focused on the regulation of TGF-β/Smad signaling pathway. However, due to the pleiotropic roles of TGF-β/Smad signaling, direct TGF-β-targeted treatments are unlikely to be therapeutically feasible in clinic. Recently, the downstream IL-11/ERK1/2 signaling of TGF-β has become an attractive therapeutic target without upstream disadvantages. Based on that, this study was designed to identify the potential effects of osthole on IL-11/ERK1/2 signaling pathway in renal fibrosis.Methods: The renal fibrosis model was established in vivo and in vitro, we investigated the effects of osthole on unilateral ureteral obstruction (UUO)-induced renal fibrosis and TGF-β-induced HK-2 cells. After preliminarily confirming the antifibrogenic effects of osthole and the link between its antifibrogenic effects and the inhibition of IL-11/ERK1/2 signaling, we applied a direct IL-11-induced HK-2 cells fibrosis model to further explore the inhibitory effects of osthole on IL-11/ERK1/2 signaling pathway.Results: Our results confirmed that osthole can decrease the secretion of fibrosis proteins, such as α-smooth muscle actin (α-SMA), collagen I, and fibronectin, ameliorate experimental renal fibrosis in vivo and in vitro, and the effect was associated with suppressing TGF-β1/Smad signaling. More importantly, we found that IL-11/ERK1/2 signaling in UUO-induced renal fibrosis and TGF-β-induced HK-2 cell model was obviously upregulated, and osthole treatment also significantly inhibited the abnormal IL-11/ERK1/2 signaling activation. Given the direct link between TGF-β/Smad signaling and IL-11/ERK1/2 signaling pathway, we have verified that osthole has a direct inhibitory effect on IL-11/ERK1/2 signaling independent of TGF-β signaling by using an IL-11-induced HK-2 cells fibrosis model. Osthole treatment decreased the protein expression of α-SMA, collagen I and fibronectin without changing their mRNA levels in IL-11-induced HK-2 cells. Moreover, it was observed that the IL-11/ERK1/2 inhibitor, U0126, partly blocked the antifibrogenic effects of osthole.Conclusion: In this study, we found that osthole has a previously unrecognized role in inhibiting IL-11/ERK1/2 signaling pathway. Our work demonstrated that the antifibrogenic effect of osthole is not only mediated by TGF-β/Smad2/3 signaling, but also directly mediated by IL-11/ERK1/2 signaling pathway independent of TGF-β1 signaling.

scholarly journals Characterization of In Vitro 3D Cell Model Developed from Human Hepatocellular Carcinoma (HepG2) Cell Line

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2557
Author(s):  
Martina Štampar ◽  
Barbara Breznik ◽  
Metka Filipič ◽  
Bojana Žegura
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Cell Model ◽  
Human Hepatocellular Carcinoma ◽  
Time Dependent ◽  
Hepg2 Cell Line ◽  
Cell Models

In genetic toxicology, there is a trend against the increased use of in vivo models as highlighted by the 3R strategy, thus encouraging the development and implementation of alternative models. Two-dimensional (2D) hepatic cell models, which are generally used for studying the adverse effects of chemicals and consumer products, are prone to giving misleading results. On the other hand, newly developed hepatic three-dimensional (3D) cell models provide an attractive alternative, which, due to improved cell interactions and a higher level of liver-specific functions, including metabolic enzymes, reflect in vivo conditions more accurately. We developed an in vitro 3D cell model from the human hepatocellular carcinoma (HepG2) cell line. The spheroids were cultured under static conditions and characterised by monitoring their growth, morphology, and cell viability during the time of cultivation. A time-dependent suppression of cell division was observed. Cell cycle analysis showed time-dependent accumulation of cells in the G0/G1 phase. Moreover, time-dependent downregulation of proliferation markers was shown at the mRNA level. Genes encoding hepatic markers, metabolic phase I/II enzymes, were time-dependently deregulated compared to monolayers. New knowledge on the characteristics of the 3D cell model is of great importance for its further development and application in the safety assessment of chemicals, food products, and complex mixtures.

scholarly journals Validation of a Quantification Method for Curcumin Derivatives and Their Hepatoprotective Effects on Nonalcoholic Fatty Liver Disease

2022 ◽  
Vol 44 (1) ◽  
pp. 409-432
Author(s):  
Young-Seob Lee ◽  
Seon Min Oh ◽  
Qian-Qian Li ◽  
Kwan-Woo Kim ◽  
Dahye Yoon ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepg2 Cell ◽  
Fatty Liver Disease ◽  
Cell Model ◽  
Therapeutic Effects ◽  
Nonalcoholic Fatty Liver ◽  
Curcumin Derivatives

Curcumin (CM), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are major curcumin derivatives found in the rhizome of turmeric (Curcuma longa L.), and have yielded impressive properties to halt various diseases. In the present study, we carried out a method validation for curcumin derivatives and analyzed the contents simultaneously using HPLC with UV detection. For validation, HPLC was used to estimate linearity, range, specificity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ). Results showed a high linearity of the calibration curve, with a coefficient of correlation (R2) for CM, DMC, and BDMC of 0.9999, 0.9999, and 0.9997, respectively. The LOD values for CM, DMC, and BDMC were 1.16, 1.03, and 2.53 ng/μL and LOQ values were 3.50, 3.11, and 7.67 ng/μL, respectively. Moreover, to evaluate the ability of curcumin derivatives to reduce liver lipogenesis and compare curcumin derivatives’ therapeutic effects, a HepG2 cell model was established to analyze their hepatoprotective properties. Regarding the in vivo study, we investigated the effect of DMC, CM, and BDMC on nonalcoholic fatty liver disease (NAFLD) caused by a methionine choline deficient (MCD)-diet in the C57BL/6J mice model. From the in vitro and in vivo results, curcumin derivatives alleviated MCD-diet-induced lipid accumulation as well as high triglyceride (TG) and total cholesterol (TC) levels, and the protein and gene expression of the transcription factors related to liver adipogenesis were suppressed. Furthermore, in MCD-diet mice, curcumin derivatives suppressed the upregulation of toll-like receptors (TLRs) and the production of pro-inflammatory cytokines. In conclusion, our findings indicated that all of the three curcuminoids exerted a hepatoprotective effect in the HepG2 cell model and the MCD-diet-induced NAFLD model, suggesting a potential for curcuminoids derived from turmeric as novel therapeutic agents for NAFLD.

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