scholarly journals Effect of a Novel High Phenolic Sorghum Bran (PI570481) on Lipid Accumulation in 3T3-L1 Cells

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1227-1227
Author(s):  
Seong-Ho Lee ◽  
Hee-Seop Lee ◽  
Ramasamy Perumal ◽  
Dmitriy Smolensky

Abstract Objectives Obesity is the leading public health problem and the main cause of many other metabolic and chronic complications. Sorghum is the fifth most important cereal crop in the world and certain varieties contain significantly greater amounts of biologically active phenolic compounds than other strains. PI570481 is a novel strain of high phenolic sorghum bran and show anti-cancer activities. The objective of this study is to explore a potential use of PI570481 with other phenolic sorghum bran extracts (SC84 and Sumac) and a sorghum grain (white sorghum) for the differentiation of preadipocytes and to investigate cellular and molecular responses in differentiated adipocytes to elucidate related mechanisms. Methods 3T3-L1 preadipocytes were cultured with DMEM containing 10% FBS and differentiated using a differentiation cocktail containing 1 μM dexamethasone, 0.5 mM isobutylmethylxanthine, and 5 μg/mL insulin in 10% FBS/DMEM. Lipid accumulation was measured by Oil Red O (ORO) staining. Cellular reactive oxygen species (ROS) and glucose uptake were measured using DCFH-DA and 2-NBDG, respectively. Western blotting was performed to examine the expression of genes regulating adipogenesis, lipogenesis and cell signaling. Results Sorghum extracts (PI570481, SC84, Sumac, white) did not cause cytotoxicity in both undifferentiated and differentiated 3T3-L1 cells. Sorghum bran extracts (PI570481, SC84, Sumac) reduced intracellular lipid accumulation and expression of adipogenic and lipogenic proteins in dose-dependent manner in differentiated 3T3-L1 cells. Regarding anti-adipogenic mechanism, sorghum bran extracts (PI570481, SC84, Sumac) represses ROS production and MAPK signaling pathways in differentiated 3T3-L1 cells. Sorghum bran extracts (PI570481, SC84, Sumac) also represses insulin signaling and glucose uptake in differentiated 3T3-L1 cells. Conclusions These data propose a potential use of a novel high phenolic sorghum bran as functional food. Funding Sources Maryland Agricultural Experiment Station (MAES) and National Institute of Food and Agriculture (Project #: MD-NFSC-201,176) to S-HL Cooperative Agreement grant from USDA-ARS to S-HL.

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1224-1224
Author(s):  
Ye Jin Kim ◽  
Gwang-woong !Go

Abstract Objectives Rottlerin is isolated from Mallotus japonicus, a rich-in polyphenol. Rottlerin is a PKC delta inhibitor known for an uncoupler of oxidative phosphorylation and anti-neoplastic agent. However, the effect of anti-obesity is not conclusive. This study hypothesized that rottlerin inhibits lipid accumulation in adipocytes. Methods 3T3-L1 cells were maintained with DMEM containing 10% BCS and 1% penicillin. The cells were seeded in a 6-well plate with a density of 8 × 104 followed by cultured for 4 days until reaching 120% confluency and incubated in a differentiation medium for 6 days. Rottlerin was incubated with differentiation media (0, 1, 2, and 4 µM). Cells were harvested after treatment for measurement of Oil Red O stating, immunoblotting, and RT-PCR. Results Differentiated 3T3-L1 adipocytes were stained using the Oil Red O, which stains triglycerides into the red. Lipid accumulation was significantly inhibited in 4 µM of rottlerin (P < 0.001). In protein levels, PPARγ, an adipogenesis marker, was reduced dose-dependently decreased (P < 0.001), indicating lipid droplet formation reduced. FAS and SCD1 were diminished by rottlerin treated groups (all P < 0.001). ACC-pS79/ACC was increased by rottlerin (P = 0.02). In mRNA gene expressions, C/EBPα was reduced by rottlerin in a dose-dependent manner (P < 0.001), and PPARγ tend to be decreased by rottlerin (P = 0.06). FAS and SREBP1 were inhibited by rottlerin (P < 0.01). SCD1 was dramatically reduced by rottlerin (P < 0.001). Conclusions We found that rottlerin reduces lipid accumulation by inhibiting adipogenesis in differentiated 3T3-L1 adipocytes. This suggests that rottlerin is a potential nutraceutical for treating dyslipidemia, non-alcoholic fatty liver disease, and obesity. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; MSIT).


2015 ◽  
Vol 4 (1) ◽  
pp. 69-73
Author(s):  
Thomas J. Rhodes ◽  
Michelle Pazienza ◽  
Jodi F. Evans

ACTH is a major hormone of the stress axis or hypothalamic-pituitary-adrenal (HPA) axis.  It is derived from pro-opiomelanocortin (POMC) the precursor to the melanocortin family of peptides. POMC produces the biologically active melanocortin peptides via a series of enzymatic steps in a tissue-specific manner, yielding the melanocyte-stimulating hormones (MSHs), corticotrophin (ACTH) and ?-endorphin. The melanocortin system plays an imperative role in energy expenditure, insulin release and insulin sensitivity.  Bone marrow derived mesenchymal stem cells circulate in the blood stream and as progenitor cells have the potential to differentiate into many cell types such as osteoblasts, chondrocytes and adipocytes. Here we examine the effects of ACTH on the mouse D1 bone-marrow derived MSC.  ACTH significantly increased lipid accumulation during the adipogenic differentiation of D1 cells in a concentration- dependent manner. ACTH also shifts the temporal pattern of D1 adipogenic differentiation to the left i.e. differentiation occurs earlier with ACTH treatment. No significant differences in protein expression of peroxisome proliferator-activated receptor gamma (PPAR-?2), a regulating transcription factor of adipogenesis were found.  Therefore the effects of ACTH are suggested to be mediated by an alternative pathway. Overall the results indicate a connection between increased adipose deposition and the elevated circulating ACTH associated with stress.


2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.


2014 ◽  
Vol 25 (3-4) ◽  
pp. 24-33
Author(s):  
O. I. Dzjuba ◽  
M. V. Yatsenko

The article deals with the history of the study and the current state of research of physiological and biochemical properties of the plant genus Sedum that are useful for human and has been used in folk medicine for many years. It was noticed that antioxidant properties of extracts from plants S. sarmentosum, S. sempervivoides, S. takesimense were caused by the presence of phenolic compounds. Methanol extract of plants S. takesimense exhibited strong scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals as well as significant inhibitory effects on lipid peroxidation and low density lipoprotein (LDL) oxidation induced by a metal ion Cu2+. Various immunomodulatory activities of various fractions of plants extracts (S. dendroideum, S. kamtschaticum, S. sarmentosum, S. telephium) are observed. It was shown that the ethanol extract of S. sarmentosum and it’s fractions suppressed specific antibody and cellular responses to ovalbumin in mice. The methanol extract of plants S. sarmentosum reduced the levels of anti-inflammatory markers, such as volume of exudates, number of polymorphonuclear leukocytes, suppressed nitric oxide synthesis in activated macrophages via suppressed induction of inducible nitric oxide synthase (iNOS). Polysaccharides fractions from plants S. telephium inducing productions of tumor necrosis factor alpha (TNF-α), increasing the intensity of phagocytosis in vitro and in vivo. Methanol extract from the whole part of S. kamtschaticum strongly inhibit PGE2 production from lipopolysaccharide-induced RAW 264.7 cells, a mouse macrophage cell line via modulating activity in gene expression of the enzyme cyclooxygenase-2 (COX-2). The methanol extract of plants S. sarmentosum and the major kaempferol glycosides from S. dendroideum have antinociceptive activity. It was noticed that anti-adipogenic activity of extracts from plants S. kamtschaticum were caused by inhibition of peroxisome-proliferator-activated receptor γ (PPARγ) expression and it’s dependent target genes, such as genes encoding adipocyte protein 2 (аР2), lipoprotein lipase (LPL), adiponectin and CD36. Polysaccharides fractions from S. telephium cause inhibition of cell adhesion of human fibroblast (MRC5) to laminin and fibronectin via interfere with integrin-mediated cell behaviour and they contributed to the role of polysaccharides in cell-matrix interaction. The methanol extract of plants S. sarmentosum exhibited a significant inhibitory activity in the chick embryo chorioallantoic membrane angiogenesis in a dose-dependent manner. The crude alkaloid fraction of S. sarmentosum caused a dose-dependent inhibition of cell proliferation on murine hepatoma cell line BNL CL.2 and human hepatoma cell line HepG2 without necrosis or apoptosis. Alkaloids from plants S. sarmentosum may improve survival of hepatoma patients via the inhibition of excessive growth of tumor cells. Plant’s juices have antiviral activity (S. sarmentosum, S. spurium, S. stahlii). Crude ethanol extract S. praealtum have spermicidal activity of the in mice and a relevant inhibitory effect of aqueous extract on human spermatozoa motility as well as an anti-fertilizing activity in rats. Hepatoprotective triterpenes, e.g., δ-amyrone, 3-epi-δ-amyrin, δ-amyrin and sarmentolin were isolated from S. sarmentosum. 2- and 2,6-substituted piperidine alkaloids (e.g., norsedamine, allosedridine, sedamine, allosedamine) are observed in plants S. acre, which in the presence of data on the use of pyridine and piperidine derivatives for treating neurodegenerative diseases (e.g., Alzheimer's disease), points on the promising research in this area. Taking into account that biologically active compounds are accumulated in the aboveground vegetative organs of plants of Sedum, the prospects of further study of the use of Sedum for the purposes of biotechnology and in the pharmaceutical industry becomes apparent. This work extends the existing views regarding the use of plants Sedum.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ke Zhang ◽  
Zhuoying Li ◽  
Yunyang Lu ◽  
Linyi Xiang ◽  
Jiadong Sun ◽  
...  

Abstract Background The Wnt planar cell polarity (PCP) pathway is implicated in osteoarthritis (OA) both in animals and in humans. Van Gogh-like 2 (Vangl2) is a key PCP protein that is required for the orientation and alignment of chondrocytes in the growth plate. However, its functional roles in OA still remain undefined. Here, we explored the effects of Vangl2 on OA chondrocyte in vitro and further elucidated the molecular mechanism of silencing Vangl2 in Wnt5a-overexpressing OA chondrocytes. Methods Chondrocytes were treated with IL-1β (10 ng/mL) to simulate the inflammatory microenvironment of OA. The expression levels of Vangl2, Wnt5a, MMPs, and related proinflammatory cytokines were measured by RT-qPCR. Small interfering RNA (siRNA) of Vangl2 and the plasmid targeting Wnt5a were constructed and transfected into ATDC5 cells. Then, the functional roles of silencing Vangl2 in the OA chondrocytes were investigated by Western blotting, RT-qPCR, and immunocytochemistry (ICC). Transfected OA chondrocytes were subjected to Western blotting to analyze the relationship between Vangl2 and related signaling pathways. Results IL-1β induced the production of Vangl2, Wnt5a, and MMPs in a time-dependent manner and the significantly increased expression of Vangl2. Vangl2 silencing effectively suppressed the expression of MMP3, MMP9, MMP13, and IL-6 at both gene and protein levels and upregulated the expression of type II collagen and aggrecan. Moreover, knockdown of Vangl2 inhibited the phosphorylation of MAPK signaling molecules (P38, ERK, and JNK) and P65 in Wnt5a-overexpressing OA chondrocytes. Conclusions For the first time, we demonstrate that Vangl2 is involved in the OA process. Vangl2 silencing can notably alleviate OA progression in vitro by inhibiting the expression of MMPs and increasing the formation of the cartilage matrix and can inhibit the proinflammatory effects of Wnt5a via MAPK and NF-κB pathway. This study provides new insight into the mechanism of cartilage inflammation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie Qu ◽  
Sarah Fourman ◽  
Maureen Fitzgerald ◽  
Min Liu ◽  
Supna Nair ◽  
...  

AbstractApolipoprotein A4 (APOA4) is one of the most abundant and versatile apolipoproteins facilitating lipid transport and metabolism. APOA4 is synthesized in the small intestine, packaged onto chylomicrons, secreted into intestinal lymph and transported via circulation to several tissues, including adipose. Since its discovery nearly 4 decades ago, to date, only platelet integrin αIIbβ3 has been identified as APOA4 receptor in the plasma. Using co-immunoprecipitation coupled with mass spectrometry, we probed the APOA4 interactome in mouse gonadal fat tissue, where ApoA4 gene is not transcribed but APOA4 protein is abundant. We demonstrate that lipoprotein receptor-related protein 1 (LRP1) is the cognate receptor for APOA4 in adipose tissue. LRP1 colocalized with APOA4 in adipocytes; it interacted with APOA4 under fasting condition and their interaction was enhanced during lipid feeding concomitant with increased APOA4 levels in plasma. In 3T3-L1 mature adipocytes, APOA4 promoted glucose uptake both in absence and presence of insulin in a dose-dependent manner. Knockdown of LRP1 abrogated APOA4-induced glucose uptake as well as activation of phosphatidylinositol 3 kinase (PI3K)-mediated protein kinase B (AKT). Taken together, we identified LRP1 as a novel receptor for APOA4 in promoting glucose uptake. Considering both APOA4 and LRP1 are multifunctional players in lipid and glucose metabolism, our finding opens up a door to better understand the molecular mechanisms along APOA4-LRP1 axis, whose dysregulation leads to obesity, cardiovascular disease, and diabetes.


2021 ◽  
Vol 22 (4) ◽  
pp. 1883
Author(s):  
Coralia Cotoraci ◽  
Alina Ciceu ◽  
Alciona Sasu ◽  
Anca Hermenean

Anemia, characterized by a decrease of the hemoglobin level in the blood and a reduction in carrying capacity of oxygen, is a major public health problem which affects people of all ages. The methods used to treat anemia are blood transfusion and oral administration of iron-based supplements, but these treatments are associated with a number of side effects, such as nausea, vomiting, constipation, and stomach pain, which limit its long-term use. In addition, oral iron supplements are poorly absorbed in the intestinal tract, due to overexpression of hepcidin, a peptide hormone that plays a central role in iron homeostasis. In this review, we conducted an analysis of the literature on biologically active compounds and plant extracts used in the treatment of various types of anemia. The purpose of this review is to provide up-to-date information on the use of these compounds and plant extracts, in order to explore their therapeutic potential. The advantage of using them is that they are available from natural resources and can be used as main, alternative, or adjuvant therapies in many diseases, such as various types of anemia.


Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2248 ◽  
Author(s):  
Jian-Ming Chen ◽  
Pei-Yin Chen ◽  
Chia-Chieh Lin ◽  
Ming-Chang Hsieh ◽  
Jen-Tsun Lin

Background: Sesamin is a lignin present in sesame oil from the bark of Zanthoxylum spp. Sesamin reportedly has anticarcinogenic potential and exerts anti-inflammatory effects on several tumors. Hypothesis/Purpose: However, the effect of sesamin on metastatic progression in human head and neck squamous carcinoma (HNSCC) remains unknown in vitro and in vivo; hence, we investigated the effect of sesamin on HNSCC cells in vitro. Methods and Results: Sesamin-treated human oral cancer cell lines FaDu, HSC-3, and Ca9-22 were subjected to a wound-healing assay. Furthermore, Western blotting was performed to assess the effect of sesamin on the expression levels of matrix metalloproteinase (MMP)-2 and proteins of the MAPK signaling pathway, including p-ERK1/2, P-p38, and p-JNK1/2. In addition, we investigated the association between MMP-2 expression and the MAPK pathway in sesamin-treated oral cancer cells. Sesamin inhibited cell migration and invasion in FaDu, Ca9-22, and HSC-3 cells and suppressed MMP-2 at noncytotoxic concentrations (0 to 40 μM). Furthermore, sesamin significantly reduced p38 MAPK and JNK phosphorylation in a dose-dependent manner in FaDu and HSC-3 cells. Conclusions: These results indicate that sesamin suppresses the migration and invasion of HNSCC cells by regulating MMP-2 and is thus a potential antimetastatic agent for treating HNSCC.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
Z Bargaoui ◽  
K Mzoughi ◽  
I Zairi ◽  
O Aouina

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Smoking is a public health problem. Doctors have an important role in the fight against smoking, in particular through the minimum advice they can give. Purpose The aim of this work was to study the prevalence of the application of minimal advice by medical residents and to identify factors that may influence its practice. Methods We conducted a descriptive and analytical study with a prospective data collection that included 302 residents practicing in Tunisia and who agreed to respond to an online questionnaire submitted between February and March 2020. Results Residents mean age was of 28 ± 2 years and the gender ratio was 0.65. Sixty-four percent of residents were non-smokers. During their practice, 94% of residents systematically identified the patient"s smoking status and 61.9% were unfamiliar with the concept of minimal advice. The rate of application of the minimum advice by residents was 57.6%. In multivariate analysis, the factors influencing the application of minimum counseling were: gender (OR =0.321, p = 0.0001), knowledge of minimum counseling (OR = 2.808, p = 0.002) and having attended the minimum advice given by a senior (OR = 2.328, p = 0.0001). Conclusion The rate of application of the minimum advice remains low. Improving one"s theoretical and practical teaching during medical studies is essential.


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