scholarly journals Puerarin Alleviates Depression-Like Behavior Induced by High-Fat Diet Combined With Chronic Unpredictable Mild Stress via Repairing TLR4-Induced Inflammatory Damages and Phospholipid Metabolism Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Li-Na Gao ◽  
Maocai Yan ◽  
Lirun Zhou ◽  
Jian’an Wang ◽  
Chunmei Sai ◽  
...  

Puerarin has been reported as a potential agent for neuro-inflammatory disorders. However, there have been no reports of using puerarin for the treatment of depression based on Toll-like receptor 4 (TLR4)–mediated inflammatory injury. In this study, we evaluated the protective effects of puerarin on depression-like rats induced by a high-fat diet (HFD) combined with chronic unpredictable mild stress (CUMS). The mechanism was screened by lipidomics and molecular docking and confirmed by in vivo tests. Puerarin treatment significantly improved 1% sucrose preference and ameliorated depression-like behavior in the open-field test. The antidepressive effects of puerarin were associated with decreased pro-inflammatory cytokine production, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and increased anti-inflammatory cytokine levels (IL-10) in rat hippocampal tissues and plasma. Hematoxylin–eosin (H&E), immunofluorescence staining, and Western blotting results displayed that puerarin alleviated inflammatory injury by suppressing TLR4 expression and by repairing the intestine mucus barrier via enhancing the expression of claudin-1 and occludin. Non-targeted lipidomics analysis showed that the most significantly different metabolites modified by puerarin were phospholipids. Puerarin treatment–altered biomarkers were identified as PC (15:1/20:1), PE (15:1/16:1), and PI (18:2/20:1) in comparison with the HFD/CUMS group. Molecular docking modeling revealed that puerarin could bind with cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2), which play central roles in TLR4-mediated phospholipid metabolism. In vivo, puerarin treatment decreased the enzyme activities of cPLA2 and COX-2, resulting in lower production of prostaglandin E2 (PGE2) in hippocampal and intestinal tissues. In conclusion, puerarin treatment reverses HFD/CUMS-induced depression-like behavior by inhibiting TLR4-mediated intestine mucus barrier dysfunction and neuro-inflammatory damages via the TLR4/cPLA2/COX-2 pathway.

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jin Ling Yang ◽  
De Xiang Liu ◽  
Hong Jiang ◽  
Fang Pan ◽  
Cyrus SH Ho ◽  
...  

2016 ◽  
Vol 12 (2) ◽  
pp. 159-166
Author(s):  
Pingting Li ◽  
Zhibin Tan ◽  
Xiaoling Gao ◽  
Shuqiang Liu ◽  
Shuling Wang

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepak Kumar Singh ◽  
Mayank Kulshreshtha ◽  
Yogesh Kumar ◽  
Pooja A Chawla ◽  
Akash Ved ◽  
...  

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.


2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4291
Author(s):  
Santina Chiechio ◽  
Magda Zammataro ◽  
Massimo Barresi ◽  
Margherita Amenta ◽  
Gabriele Ballistreri ◽  
...  

Citrus fruits are a rich source of high-value bioactive compounds and their consumption has been associated with beneficial effects on human health. Red (blood) oranges (Citrus sinensis L. Osbeck) are particularly rich in anthocyanins (95% of which are represented by cyanidin-3-glucoside and cyanidin-3-6″-malonyl-glucoside), flavanones (hesperidin, narirutin, and didymin), and hydroxycinnamic acids (caffeic acid, coumaric acid, sinapic, and ferulic acid). Lemon fruit (Citrus limon) is also rich in flavanones (eriocitrin, hesperidin, and diosmin) and other polyphenols. All of these compounds are believed to play a very important role as dietary antioxidants due to their ability to scavenge free radicals. A standardized powder extract, red orange and lemon extract (RLE), was obtained by properly mixing anthocyanins and other polyphenols recovered from red orange processing waste with eriocitrin and other flavanones recovered from lemon peel by a patented extraction process. RLE was used for in vivo assays aimed at testing a potential beneficial effect on glucose and lipid metabolism. In vivo experiments performed on male CD1 mice fed with a high-fat diet showed that an 8-week treatment with RLE was able to induce a significant reduction in glucose, cholesterol and triglycerides levels in the blood, with positive effects on regulation of hyperglycemia and lipid metabolism, thus suggesting a potential use of this new phytoextract for nutraceutical purposes.


2017 ◽  
Vol 43 (5) ◽  
pp. 1961-1973 ◽  
Author(s):  
Yan Bai ◽  
Zhenli Su ◽  
Hanqi Sun ◽  
Wei Zhao ◽  
Xue Chen ◽  
...  

Background/Aims: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. Methods: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups. Normal diet was given to rats in the control group, high-fat diet was given to rats in HFD and AE-treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total cholesterol and triglyceride levels were measured to validate the HFD model. Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp technique were applied to examine cardiac electrical activity, action potential and inward rectifier K+ current (IK1), respectively. Neonatal rat ventricular myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR in vivo and in vitro, respectively. Results: In vivo, AE significantly shortened the QT interval, action potential duration at 90% repolarization (APD90) and resting membrane potential (RMP), which were markedly elongated by HFD. AE increased IK1 current and Kir2.1 protein expression which were reduced in HFD rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. Conclusions: AE prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD-induced cardiac electrical remodeling.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jaime Gonzalez ◽  
Wendy Donoso ◽  
Natalia Díaz ◽  
María Eliana Albornoz ◽  
Ricardo Huilcaman ◽  
...  

Cardiovascular diseases (CVD) represent about 30% of all global deaths. It is currently accepted that, in the atherogenic process, platelets play an important role, contributing to endothelial activation and modulation of the inflammatory phenomenon, promoting the beginning and formation of lesions and their subsequent thrombotic complications. The objective of the present work was to study using immunohistochemistry, the presence of platelets, monocytes/macrophages, and cell adhesion molecules (CD61, CD163, and CD54), in two stages of the atheromatous process. CF-1 mice fed a fat diet were used to obtain early stages of atheromatous process, denominated early stage of atherosclerosis, and ApoE−/−mice fed a fat diet were used to observe advanced stages of atherosclerosis. The CF-1 mice model presented immunostaining on endothelial surface for all three markers studied; the advanced atherosclerosis model in ApoE−/−mice also presented granular immunostaining on lesion thickness, for the same markers. These results suggest that platelets participate in atheromatous process from early stages to advance d stages. High fat diet induces adhesion of platelets to endothelial cellsin vivo. These findings support studying the participation of platelets in the formation of atheromatous plate.


Nutrients ◽  
2015 ◽  
Vol 7 (8) ◽  
pp. 6313-6329 ◽  
Author(s):  
Kampeebhorn Boonloh ◽  
Veerapol Kukongviriyapan ◽  
Bunkerd Kongyingyoes ◽  
Upa Kukongviriyapan ◽  
Supawan Thawornchinsombut ◽  
...  

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3198 ◽  
Author(s):  
Padmamalini Baskaran ◽  
Kyle Covington ◽  
Jane Bennis ◽  
Adithya Mohandass ◽  
Teresa Lehmann ◽  
...  

(1) Background: Capsaicin, a chief ingredient of natural chili peppers, enhances metabolism and energy expenditure and stimulates the browning of white adipose tissue (WAT) and brown fat activation to counter diet-induced obesity. Although capsaicin and its nonpungent analogs are shown to enhance energy expenditure, their efficiency to bind to and activate their receptor—transient receptor potential vanilloid subfamily 1 (TRPV1)—to mediate thermogenic effects remains unclear. (2) Methods: We analyzed the binding efficiency of capsaicin analogs by molecular docking. We fed wild type mice a normal chow or high fat diet (± 0.01% pungent or nonpungent capsaicin analog) and isolated inguinal WAT to analyze the expression of thermogenic genes and proteins. (3) Results: Capsaicin, but not its nonpungent analogs, efficiently binds to TRPV1, prevents high fat diet-induced weight gain, and upregulates thermogenic protein expression in WAT. Molecular docking studies indicate that capsaicin exhibits the highest binding efficacy to TRPV1 because it has a hydrogen bond that anchors it to TRPV1. Capsiate, which lacks the hydrogen bond, and therefore, does not anchor to TRPV1. (4) Conclusions: Long-term activation of TRPV1 is imminent for the anti-obesity effect of capsaicin. Efforts to decrease the pungency of capsaicin will help in advancing it to mitigate obesity and metabolic dysfunction in humans.


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